2 safety notices
Genetic variations that may affect drug response
2 known genetic variations may influence how your body responds to Sildenafil 40mg/50ml solution for injection vials.Genes involved: ACE, GNB3
These are known genetic variations. They don't mean the medicine won't work for you — speak to your doctor or a pharmacogenomics specialist for personalised advice. Source: DrugBank (CC BY-NC 4.0).
Safety information for pregnancy and breastfeeding
Pregnancy
Due to the lack of data on the effect of sildenafil indicated for the treatment of pulmonary arterial hypertension (PAH) in pregnant women, sildenafil is not recommended for women of childbearing potential unless also using appropriate contraceptive measures [F3850, F3859, F3883, L5614].
Breastfeeding
Caution should ultimately be exercised when sildenafil is administered to nursing women as it is not known if sildenafil or its metabolites are excreted in human breast milk [F3850, F3859, F3883, L5614].
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
Report a side effect
Submit a Yellow Card report to the MHRA
Official medicine documents
Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
Yellow Card reports
MHRA
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
View Drug Analysis Profile
Suspected adverse reactions reported for Sildenafil
Browse all iDAP reports
Interactive Drug Analysis Profiles for all medicines
Report a side effect
Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
EMA
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
View EudraVigilance report
Suspected adverse reactions reported for Sildenafil
About EudraVigilance
Learn about EU pharmacovigilance and safety monitoring
EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
1 branded products available
Show details
Therapeutically similar medicines
Show details
Sildenafil 50mg orodispersible films sugar free
Other
50mg
Same therapeutic group
Sildenafil 75mg orodispersible films sugar free
Other
75mg
Same therapeutic group
Sildenafil 100mg orodispersible films sugar free
Other
100mg
Same therapeutic group
Sildenafil 12.5mg/dose oromucosal spray sugar free
Spray
12.5mg
Same therapeutic group
Sildenafil 20mg/5ml oral suspension
Oral suspension
20mg/5ml
Same therapeutic group
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
Clinical guidelines and formulary information
British National Formulary
Sildenafil
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(4)
Digital ulcers: sildenafil (ESUOM42)
ESUOM42
Evidence summary
Updated Mar 2015Idiopathic pulmonary fibrosis in adults: diagnosis and management (CG163)
CG163
Clinical guideline
Updated May 2017Erectile dysfunction: avanafil (ESNM45)
ESNM45
Evidence summary
Updated Aug 2014Gastroparesis in adults: oral erythromycin (ESUOM13)
ESUOM13
Evidence summary
Updated Jun 2013Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Show details
Pharmacy stock checkers
Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
Show details
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Show details
Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
254 found
Half-life
3 to 5 hours
Mechanism
Sildenafil is an oral therapy for erectile dysfunction [A175582, F3853, F3856, F3886, L5611].
Food interactions
1 warning
Human targets
6 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
30-120 minutes
Sildenafil is known to be quickly absorbed, with maximum plasma concentrations being observed within 30-120 minutes (with a median of 60 minutes)…
Half-life
3 to 5 hours
The terminal phase half-life observed for sildenafil is approximately 3 to 5 hours [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Protein binding
96%
It is generally observed that sildenafil and its main circulating N-desmethyl metabolite are both estimated to be about 96% bound to plasma proteins…
Volume of distribution
105 L
The mean steady-state volume of distribution documented for sildenafil is approximately 105 L - a value which suggests the medication undergoes…
Metabolism
50%
The metabolism of sildenafil is facilitated primarily by the CYP3A4 hepatic microsomal isoenzymes and to a minor extent, via the CYP2C9 hepatic…
Elimination
80%
After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered…
Clearance
41 L/h
The total body clearance documented for sildenafil is 41 L/h [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
In eliciting its mechanism of action, sildenafil ultimately prevents or minimizes the breakdown of cyclic guanosine monophosphate (cGMP) by inhibiting cGMP specific phosphodiesterase type 5 (PDE5) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The result of doing so allows cGMP present in both the penis and pulmonary vasculature to elicit smooth muscle relaxation and vasodilation that subsequently facilitates relief in pulmonary arterial hypertension and the increased flow of blood into the spongy erectile tissue of the penis that consequently allows it to grow in size and become erect and rigid [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Interestingly enough, it is precisely via this mechanism why sildenafil was at first researched as a potential treatment for angina - or chest pain associated with inadequate blood flow to the heart - before being serendipitously indicated for treating erectile dysfunction in the late 1980s [A175732]. Nevertheless, it is because of this mechanism that sildenafil is also indicated for treating pulmonary arterial hypertension but is also additionally notorious for interacting with various anti-anginal or anti-hypertensive agents to develop potentially rapid, excessive, and/or fatal hypotensive crises [A175579][A175582][A175654].
Regardless, sildenafil, among a variety of other similar or related PDE5 inhibitors, has become a common and effective treatment for erectile dysfunction and since its formal approval for medical use in the public in 1998 [A175732], continues to see millions of prescriptions written for it internationally. Although the medication has historically been most popularly recognized as Pfizer's brand name Viagra, sildenafil is currently available generically and even as a non-prescription over the counter medication in some countries [L5656].
Interestingly enough, it is precisely via this mechanism why sildenafil was at first researched as a potential treatment for angina - or chest pain associated with inadequate blood flow to the heart - before being serendipitously indicated for treating erectile dysfunction in the late 1980s [A175732]. Nevertheless, it is because of this mechanism that sildenafil is also indicated for treating pulmonary arterial hypertension but is also additionally notorious for interacting with various anti-anginal or anti-hypertensive agents to develop potentially rapid, excessive, and/or fatal hypotensive crises [A175579][A175582][A175654].
Regardless, sildenafil, among a variety of other similar or related PDE5 inhibitors, has become a common and effective treatment for erectile dysfunction and since its formal approval for medical use in the public in 1998 [A175732], continues to see millions of prescriptions written for it internationally. Although the medication has historically been most popularly recognized as Pfizer's brand name Viagra, sildenafil is currently available generically and even as a non-prescription over the counter medication in some countries [L5656].
Properties:
View FDA drug labelsolid
Avg. mass: 474.58 Da
DrugBank indication
Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor that is predominantly employed for two primary indications:
(1) the treatment of erectile dysfunction [A175582, L5611, F3853, F3856, F3886]; and
(2) treatment of pulmonary hypertension, where:
a) the US FDA specifically indicates sildenafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening F3850. The delay in clinical worsening was demonstrated when sildenafil was added to background epoprostenol therapy F3850. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%) F3850;
b) the Canadian product monograph specifically indicates sildenafil for the treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease (CTD) in adult patients with WHO functional class II or III who have not responded to conventional therapy F3859.
In addition, improvement in exercise ability and delay in clinical worsening was demonstrated in adult patients who were already stabilized on background epoprostenol therapy F3859; and
c) the EMA product information specifically indicates sildenafil for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity F3883. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease F3883. The EMA label also indicates sildenafil for the treatment of pediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension F3883.
Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease F3883.
(1) the treatment of erectile dysfunction [A175582, L5611, F3853, F3856, F3886]; and
(2) treatment of pulmonary hypertension, where:
a) the US FDA specifically indicates sildenafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening F3850. The delay in clinical worsening was demonstrated when sildenafil was added to background epoprostenol therapy F3850. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%) F3850;
b) the Canadian product monograph specifically indicates sildenafil for the treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease (CTD) in adult patients with WHO functional class II or III who have not responded to conventional therapy F3859.
In addition, improvement in exercise ability and delay in clinical worsening was demonstrated in adult patients who were already stabilized on background epoprostenol therapy F3859; and
c) the EMA product information specifically indicates sildenafil for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity F3883. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease F3883. The EMA label also indicates sildenafil for the treatment of pediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension F3883.
Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease F3883.
Also known as(127)
1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine
Sildenafil
Sildenafilo
3.1.4.35
CGB-PDE
cGMP-binding cGMP-specific phosphodiesterase
PDE5
C1 esterase inhibitor
Dosage forms(104)
Tablet, film coated (Oral) — 140.5 MG
Tablet (Oral) — 25 mg
Tablet (Oral) — 50.000 mg
Tablet (Oral) — 140.48 mg
Suspension (Oral) — 25 MG/ML
Film, soluble; injection, suspension (Oral) — 50 mg
Tablet, chewable (Oral) — 5000000 mg
Tablet, film coated (Oral)
Molecular properties(19)
Drug interactions(1213)
Known interactions with other medications. Always consult a healthcare professional.
The serum concentration of Afatinib can be increased when it is combined with Sildenafil.
The serum concentration of Bosutinib can be increased when it is combined with Sildenafil.
Brentuximab vedotin
Unknown severity
The serum concentration of Brentuximab vedotin can be increased when it is combined with Sildenafil.
Colchicine
Unknown severity
The serum concentration of Colchicine can be increased when it is combined with Sildenafil.
The serum concentration of Edoxaban can be increased when it is combined with Sildenafil.
Ledipasvir
Unknown severity
The serum concentration of Ledipasvir can be increased when it is combined with Sildenafil.
The serum concentration of Naloxegol can be increased when it is combined with Sildenafil.
The serum concentration of Pazopanib can be increased when it is combined with Sildenafil.
Prucalopride
Unknown severity
The serum concentration of Prucalopride can be increased when it is combined with Sildenafil.
Ranolazine
Unknown severity
The serum concentration of Ranolazine can be increased when it is combined with Sildenafil.
The excretion of Silodosin can be decreased when combined with Sildenafil.
The serum concentration of Topotecan can be increased when it is combined with Sildenafil.
Cilostazol
Unknown severity
The serum concentration of Cilostazol can be increased when it is combined with Sildenafil.
Everolimus
Unknown severity
The serum concentration of Everolimus can be increased when it is combined with Sildenafil.
The serum concentration of Rifaximin can be increased when it is combined with Sildenafil.
Erythromycin
Moderate
The metabolism of Sildenafil can be decreased when combined with Erythromycin.
Alprostadil
Major
The risk or severity of hypotension and priapism can be increased when Sildenafil is combined with Alprostadil.
Amyl Nitrite
Major
The risk or severity of hypotension can be increased when Amyl Nitrite is combined with Sildenafil.
Boceprevir
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Boceprevir.
Fluconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Fluconazole.
Voriconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Voriconazole.
Ketoconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Ketoconazole.
Miconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Miconazole.
Itraconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Itraconazole.
Posaconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Posaconazole.
The serum concentration of Sildenafil can be increased when it is combined with Abafungin.
Ravuconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Ravuconazole.
Isavuconazonium
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Isavuconazonium.
Isavuconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Isavuconazole.
Albaconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Albaconazole.
Bifonazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Bifonazole.
Levoketoconazole
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Levoketoconazole.
Mirabegron
Unknown severity
The serum concentration of Sildenafil can be increased when it is combined with Mirabegron.
Sapropterin
Moderate
Sapropterin may increase the hypotensive activities of Sildenafil.
Eluxadoline
Unknown severity
The serum concentration of Eluxadoline can be increased when it is combined with Sildenafil.
Vincristine
Unknown severity
The excretion of Vincristine can be decreased when combined with Sildenafil.
Doxorubicin
Unknown severity
The serum concentration of Doxorubicin can be increased when it is combined with Sildenafil.
Ethanol may increase the hypotensive activities of Sildenafil.
Sildenafil may increase the antihypertensive activities of Ramipril.
Sildenafil may increase the antihypertensive activities of Esmolol.
Sildenafil may increase the antihypertensive activities of Betaxolol.
Sildenafil may increase the antihypertensive activities of Remikiren.
Bethanidine
Moderate
Sildenafil may increase the antihypertensive activities of Bethanidine.
Sildenafil may increase the antihypertensive activities of Guanadrel.
Olmesartan
Moderate
Sildenafil may increase the antihypertensive activities of Olmesartan.
Chlorthalidone
Moderate
Sildenafil may increase the antihypertensive activities of Chlorthalidone.
Nitroprusside
Moderate
Sildenafil may increase the antihypertensive activities of Nitroprusside.
Sildenafil may increase the antihypertensive activities of Atenolol.
Sildenafil may increase the antihypertensive activities of Minoxidil.
Treprostinil
Moderate
Sildenafil may increase the antihypertensive activities of Treprostinil.
Showing 50 of 1213 interactions
Food & lifestyle interactions
Advice
Take with or without food. If taken with a high-fat meal the medicine may take a little longer to start working.
Toxicity & overdose
In single-dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Doses of 200 mg did not result in increased efficacy but the incidence of adverse reaction (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Due to the lack of data on the effect of sildenafil indicated for the treatment of pulmonary arterial hypertension (PAH) in pregnant women, sildenafil is not recommended for women of childbearing potential unless also using appropriate contraceptive measures [F3850, F3859, F3883, L5614].
The safety and efficacy of sildenafil indicated for treating PAH in a woman during labor and delivery have not been studied [F3850, F3859, F3883, L5614]. Caution should ultimately be exercised when sildenafil is administered to nursing women as it is not known if sildenafil or its metabolites are excreted in human breast milk [F3850, F3859, F3883, L5614].
The safety and efficacy of sildenafil for the treatment of PAH in children below 1 year of age has not been established as no data is available F3883.
Clinical experience with the elderly population in the use of sildenafil for the treatment of PAH has been varied.
Some reports suggest that there are no identified differences in responses between elderly and younger patients F3850 while others have documented that clinical efficacy as measured by 6-minute walk distance could be less in elderly patients .
[L5614]
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy F3850.
Conversely, when sildenafil was used to treat erectile dysfunction in healthy elderly volunteers (65 years or over), a reduced clearance of sildenafil was observed [F3853, L5611]. This reduction resulted in about 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years) [F3853, L5611]. Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40% [F3853, L5611].
Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42- times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m2 basis [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Due to the lack of data on the effect of sildenafil indicated for the treatment of pulmonary arterial hypertension (PAH) in pregnant women, sildenafil is not recommended for women of childbearing potential unless also using appropriate contraceptive measures [F3850, F3859, F3883, L5614].
The safety and efficacy of sildenafil indicated for treating PAH in a woman during labor and delivery have not been studied [F3850, F3859, F3883, L5614]. Caution should ultimately be exercised when sildenafil is administered to nursing women as it is not known if sildenafil or its metabolites are excreted in human breast milk [F3850, F3859, F3883, L5614].
The safety and efficacy of sildenafil for the treatment of PAH in children below 1 year of age has not been established as no data is available F3883.
Clinical experience with the elderly population in the use of sildenafil for the treatment of PAH has been varied.
Some reports suggest that there are no identified differences in responses between elderly and younger patients F3850 while others have documented that clinical efficacy as measured by 6-minute walk distance could be less in elderly patients .
[L5614]
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy F3850.
Conversely, when sildenafil was used to treat erectile dysfunction in healthy elderly volunteers (65 years or over), a reduced clearance of sildenafil was observed [F3853, L5611]. This reduction resulted in about 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years) [F3853, L5611]. Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40% [F3853, L5611].
Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42- times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m2 basis [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
How it works
Mechanism of action
Sildenafil is an oral therapy for erectile dysfunction [A175582, F3853, F3856, F3886, L5611]. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis [A175582, F3853, F3856, F3886, L5611].
The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation [A175582, F3853, F3856, F3886, L5611]. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood [A175582, F3853, F3856, F3886, L5611].
Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP [A175582, F3853, F3856, F3886, L5611]. Sildenafil has a peripheral site of action on erections [A175582, F3853, F3856, F3886, L5611]. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue [A175582, F3853, F3856, F3886, L5611]. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP [A175582, F3853, F3856, F3886, L5611]. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects [A175582, F3853, F3856, F3886, L5611].
Moreover, apart from the presence of PDE5 in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature [A175579, F3850, F3859, F3883, L5614]. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation [A175579, F3850, F3859, F3883, L5614]. In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation [A175579, F3850, F3859, F3883, L5614].
The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation [A175582, F3853, F3856, F3886, L5611]. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood [A175582, F3853, F3856, F3886, L5611].
Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP [A175582, F3853, F3856, F3886, L5611]. Sildenafil has a peripheral site of action on erections [A175582, F3853, F3856, F3886, L5611]. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue [A175582, F3853, F3856, F3886, L5611]. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP [A175582, F3853, F3856, F3886, L5611]. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects [A175582, F3853, F3856, F3886, L5611].
Moreover, apart from the presence of PDE5 in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature [A175579, F3850, F3859, F3883, L5614]. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation [A175579, F3850, F3859, F3883, L5614]. In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation [A175579, F3850, F3859, F3883, L5614].
Pharmacodynamics
In vitro studies have shown that sildenafil is selective for phosphodiesterase-5 (PDE5) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Its effect is more potent on PDE5 than on other known phosphodiesterases [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. In particular, there is a 10-times selectivity over PDE6 which is involved in the phototransduction pathway in the retina [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. There is an 80-times selectivity over PDE1, and over 700-times over PDE 2, 3, 4, 7, 8, 9, 10 and 11 [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. And finally, sildenafil has greater than 4,000-times selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (via the use of RigiScan®), after sildenafil administration compared with placebo [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Most studies assessed the efficacy of sildenafil approximately 60 minutes post-dose [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Sildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of cases, do not translate into clinical effects [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. After chronic dosing of 80 mg, three times a day to patients with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was a decrease of 9.4 mmHg and 9.1 mmHg respectively [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. After chronic dosing of 80 mg, three times a day to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were observed (a reduction in both systolic and diastolic pressure of 2 mmHg)[F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614] . At the recommended dose of 20 mg three times a day no reductions in systolic or diastolic pressure were seen [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no clinically relevant effects on the ECG were reported either [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (> 70 % stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7 % and 6 % respectively compared to baseline [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Mean pulmonary systolic blood pressure decreased by 9% [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Sildenafil showed no effect on cardiac output and did not impair blood flow through the stenosed coronary arteries [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Mild and transient differences in color discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The postulated mechanism for this change in color discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Sildenafil has no effect on visual acuity or contrast sensitivity. In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n = 9), sildenafil (single dose, 100 mg) demonstrated no significant changes in visual tests conducted (which included visual acuity, Amsler grid, color discrimination simulated traffic light, and the Humphrey perimeter and photostress test) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (via the use of RigiScan®), after sildenafil administration compared with placebo [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Most studies assessed the efficacy of sildenafil approximately 60 minutes post-dose [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Sildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of cases, do not translate into clinical effects [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. After chronic dosing of 80 mg, three times a day to patients with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was a decrease of 9.4 mmHg and 9.1 mmHg respectively [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. After chronic dosing of 80 mg, three times a day to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were observed (a reduction in both systolic and diastolic pressure of 2 mmHg)[F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614] . At the recommended dose of 20 mg three times a day no reductions in systolic or diastolic pressure were seen [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no clinically relevant effects on the ECG were reported either [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (> 70 % stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7 % and 6 % respectively compared to baseline [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Mean pulmonary systolic blood pressure decreased by 9% [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Sildenafil showed no effect on cardiac output and did not impair blood flow through the stenosed coronary arteries [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Mild and transient differences in color discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The postulated mechanism for this change in color discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Sildenafil has no effect on visual acuity or contrast sensitivity. In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n = 9), sildenafil (single dose, 100 mg) demonstrated no significant changes in visual tests conducted (which included visual acuity, Amsler grid, color discrimination simulated traffic light, and the Humphrey perimeter and photostress test) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Sildenafil is known to be quickly absorbed, with maximum plasma concentrations being observed within 30-120 minutes (with a median of 60 minutes) of oral administration in a fasting patient [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Moreover, the mean absolute bioavailability observed for sildenafil is about 41% (from a range of 25-63%) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. In particular, after oral three times a day dosing of sildenafil, the AUC and Cmax increase in proportion with dose over the recommended dosage range of 25-100 mg [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
When used in pulmonary arterial hypertension patients, however, the oral bioavailability of sildenafil after a dosing regimen of 80 mg three times a day, was on average 43% greater than compared to the lower doses [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Finally, if sildenafil is administered orally with food, the rate of absorption is observed to be decreased with a mean delay in Tmax of about 60 minutes and a mean decrease in Cmax of approximately 29% [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Regardless, the extent of absorption is not observed to be significantly affected as the recorded AUC decreased by only about 11 % [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
When used in pulmonary arterial hypertension patients, however, the oral bioavailability of sildenafil after a dosing regimen of 80 mg three times a day, was on average 43% greater than compared to the lower doses [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Finally, if sildenafil is administered orally with food, the rate of absorption is observed to be decreased with a mean delay in Tmax of about 60 minutes and a mean decrease in Cmax of approximately 29% [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Regardless, the extent of absorption is not observed to be significantly affected as the recorded AUC decreased by only about 11 % [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Half-life
The terminal phase half-life observed for sildenafil is approximately 3 to 5 hours [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Protein binding
It is generally observed that sildenafil and its main circulating N-desmethyl metabolite are both estimated to be about 96% bound to plasma proteins [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Nevertheless, it has been determined that protein binding for sildenafil is independent of total drug concentrations [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Volume of distribution
The mean steady-state volume of distribution documented for sildenafil is approximately 105 L - a value which suggests the medication undergoes distribution into the tissues [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Metabolism
The metabolism of sildenafil is facilitated primarily by the CYP3A4 hepatic microsomal isoenzymes and to a minor extent, via the CYP2C9 hepatic isoenzymes [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The predominant circulating metabolite results from the N-demethylation of sildenafil [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. This particular resultant metabolite possesses a phosphodiesterase selectivity that is similar to the parent sildenafil molecule and a corresponding in vitro potency for PDE5 that is approximately 50% that of the parent drug [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Moreover, plasma concentrations of the metabolite are about 40% of those recorded for sildenafil, a percentage that accounts for about 20% of sildenafil’s pharmacologic effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. This primary N-desmethyl metabolite of sildenafil also undergoes further metabolism, with a terminal half-life of about 4 hours [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
In patients with pulmonary arterial hypertension, plasma concentrations of the primary N-desmethyl metabolite are about 72% those of the original parent sildenafil molecule after a regimen of 20 mg three times a day - which is consequently responsible for about a 36% contribution to sildenafil’s overall pharmacological effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Moreover, plasma concentrations of the metabolite are about 40% of those recorded for sildenafil, a percentage that accounts for about 20% of sildenafil’s pharmacologic effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. This primary N-desmethyl metabolite of sildenafil also undergoes further metabolism, with a terminal half-life of about 4 hours [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
In patients with pulmonary arterial hypertension, plasma concentrations of the primary N-desmethyl metabolite are about 72% those of the original parent sildenafil molecule after a regimen of 20 mg three times a day - which is consequently responsible for about a 36% contribution to sildenafil’s overall pharmacological effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Route of elimination
After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Clearance
The total body clearance documented for sildenafil is 41 L/h [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
Drug targets(6)
Proteins and enzymes this drug interacts with in the body
cGMP-specific 3',5'-cyclic phosphodiesterase
PDE5A
inhibitor
Specific function3',5'-cyclic-AMP phosphodiesterase activity
General function & pharmacology
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP .
PMID:15489334 PMID:9714779
Specifically regulates nitric-oxide-generated cGMP PMID:15489334
PMID:15489334 PMID:9714779
Specifically regulates nitric-oxide-generated cGMP PMID:15489334
Plasma protease C1 inhibitor
SERPING1
modulator
Specific functionserine-type endopeptidase inhibitor activity
Cellular location
Secreted
General function & pharmacology
Serine protease inhibitor, which acrs as a regulator of the classical complement pathway .
PMID:10946292 PMID:11527969 PMID:3458172 PMID:6416294
Forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases .
PMID:10946292 PMID:3458172 PMID:6416294
May also regulate blood coagulation, fibrinolysis and the generation of kinins .
PMID:8495195
Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein PMID:8495195
PMID:10946292 PMID:11527969 PMID:3458172 PMID:6416294
Forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases .
PMID:10946292 PMID:3458172 PMID:6416294
May also regulate blood coagulation, fibrinolysis and the generation of kinins .
PMID:8495195
Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein PMID:8495195
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
PDE6G
inhibitor
Specific function3',5'-cyclic-GMP phosphodiesterase activity
General function & pharmacology
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones
Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
PDE6H
inhibitor
Specific function3',5'-cyclic-GMP phosphodiesterase activity
General function & pharmacology
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones
Ornithine decarboxylase
ODC1
downregulator
Specific functionornithine decarboxylase activity
General function & pharmacology
Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis
Metabolizing enzymes(7)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP3A4Cytochrome P450 3A4
substrate
CYP3A5Cytochrome P450 3A5
substrate
CYP3A7Cytochrome P450 3A7
substrate
CYP2C9Cytochrome P450 2C9
substrate
inhibitor
CYP2C19Cytochrome P450 2C19
substrate
inhibitor
CYP2D6Cytochrome P450 2D6
substrate
CYP2E1Cytochrome P450 2E1
substrate
inhibitor
Transporters(5)
Proteins that transport this drug across cell membranes
ATP-binding cassette sub-family C member 4
ABCC4
inhibitor
Specific function15-hydroxyprostaglandin dehydrogenase (NAD+) activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins .
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
ATP-binding cassette sub-family C member 5
ABCC5
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) .
PMID:10893247 PMID:12637526 PMID:12695538 PMID:15899835 PMID:17229149 PMID:25964343
Also acts as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins .
PMID:26515061
Confers resistance to the antiviral agent PMEA .
PMID:12695538
Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated .
PMID:10840050 PMID:12435799 PMID:12695538 PMID:15899835
Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway .
PMID:24836561
May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity)
PMID:10893247 PMID:12637526 PMID:12695538 PMID:15899835 PMID:17229149 PMID:25964343
Also acts as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins .
PMID:26515061
Confers resistance to the antiviral agent PMEA .
PMID:12695538
Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated .
PMID:10840050 PMID:12435799 PMID:12695538 PMID:15899835
Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway .
PMID:24836561
May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity)
ATP-binding cassette sub-family C member 10
ABCC10
inhibitor
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Lipophilic anion transporter that mediates ATP-dependent transport of glucuronide conjugates such as estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) .
PMID:12527806 PMID:15256465
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs, such as, docetaxel and paclitaxel .
PMID:15256465 PMID:23087055
Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP PMID:12527806
PMID:12527806 PMID:15256465
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs, such as, docetaxel and paclitaxel .
PMID:15256465 PMID:23087055
Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP PMID:12527806
Solute carrier organic anion transporter family member 1B1
SLCO1B1
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
ATP-dependent translocase ABCB1
ABCB1
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Scientific references(7)
Boolell M., Allen M.J., Ballard S.A., Gepi-Attee S., Muirhead G.J., Naylor A.M., Osterloh I.H., Gingell C.
Sildenafil, a novel effective oral therapy for male erectile dysfunction.
British Journal of Urology
199678(2):257-261. doi: 10.1046/j.1464-410x.1996.10220.x
Cheitlin M.D., Hutter AM Jr, Brindis R.G., Ganz P., Kaul S., Russell RO Jr, Zusman R.M.
Use of sildenafil (Viagra) in patients with cardiovascular disease.
Journal of the American College of Cardiology
199933(1):273-282. doi: 10.1016/s0735-1097(98)00656-1
Fries R., Shariat K., von Wilmowsky H., Bohm M.
Sildenafil in the Treatment of Raynaud’s Phenomenon Resistant to Vasodilatory Therapy.
Circulation
2005112(19):2980-2985. doi: 10.1161/circulationaha.104.523324
Unegbu C., Noje C., Coulson J.D., Segal J.B., Romer L.
Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors.
Pediatrics
2017 Mar139(3). pii: peds.2016-1450. doi: 10.1542/peds.2016-1450
Gong B., Ma M., Xie W., Yang X., Huang Y., Sun T., Luo Y., Huang J.
Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis.
International Urology Nephrol
2017 Oct49(10):1731-1740. doi: 10.1007/s11255-017-1644-5. Epub 2017 Jul 24
Nichols D.J., Muirhead G.J., Harness J.A.
Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality.
British Journal of Clinical Pharmacology
200253(s1). doi: 10.1046/j.0306-5251.2001.00027.x
Goldstein I., Burnett A.L., Rosen R.C., Park P.W., Stecher V.J.
The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction.
Sex Medicine Review
2019 Jan7(1):115-128. doi: 10.1016/j.sxmr.2018.06.005. Epub 2018 Oct 6
ATC classification(2 codes)
ATC G01AE10
ATC G04BE03
Affected organisms(1)
Humans and other mammals
Salt forms(1)
Sildenafil citrate(DBSALT000347)
Experimental properties(3)
Commercial products(620)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Sildenafil
Additional database identifiers
Drugs Product Database (DPD)
11854
ChemSpider
5023
BindingDB
50238854
PDB
VIA
ZINC
ZINC000019796168
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8784
GenAtlas
PDE5A
GeneCards
PDE5A
GenBank Gene Database
AF043731
GenBank Protein Database
3420185
Guide to Pharmacology
1304
UniProt Accession
PDE5A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1228
GenAtlas
SERPING1
GeneCards
SERPING1
GenBank Gene Database
X54486
UniProt Accession
IC1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8789
GeneCards
PDE6G
GenBank Gene Database
M36476
GenBank Protein Database
189703
UniProt Accession
CNRG_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8790
GeneCards
PDE6H
GenBank Gene Database
D45399
GenBank Protein Database
1311544
UniProt Accession
CNCG_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8109
GenAtlas
ODC1
GeneCards
ODC1
GenBank Gene Database
M16650
GenBank Protein Database
29893806
Guide to Pharmacology
1276
UniProt Accession
DCOR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:17635
GenAtlas
CD274
GeneCards
CD274
GenBank Gene Database
BC113736
UniProt Accession
PD1L1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2638
GenAtlas
CYP3A5
GeneCards
CYP3A5
GenBank Gene Database
J04813
GenBank Protein Database
181346
Guide to Pharmacology
1338
UniProt Accession
CP3A5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2640
GeneCards
CYP3A7
GenBank Gene Database
D00408
GenBank Protein Database
220149
UniProt Accession
CP3A7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2625
GenAtlas
CYP2D6
GeneCards
CYP2D6
GenBank Gene Database
M20403
GenBank Protein Database
181350
Guide to Pharmacology
1329
UniProt Accession
CP2D6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2631
GeneCards
CYP2E1
GenBank Gene Database
J02625
GenBank Protein Database
181360
Guide to Pharmacology
1330
UniProt Accession
CP2E1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:55
GenAtlas
ABCC4
GeneCards
ABCC4
GenBank Gene Database
AF071202
GenBank Protein Database
3335173
Guide to Pharmacology
782
UniProt Accession
MRP4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:56
GeneCards
ABCC5
GenBank Gene Database
AF104942
GenBank Protein Database
4140698
Guide to Pharmacology
783
UniProt Accession
MRP5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:52
GeneCards
ABCC10
GenBank Gene Database
AY032599
GenBank Protein Database
21103955
UniProt Accession
MRP7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10959
GenAtlas
SLCO1B1
GeneCards
SLCO1B1
GenBank Gene Database
AF060500
GenBank Protein Database
5051630
Guide to Pharmacology
1220
UniProt Accession
SO1B1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
International reference pricing
6 formulations
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
From $9.33/ml
To $24.38/g
Revatio 10 mg/12.5 ml vial
$9.33/ml
Revatio 20 mg tablet
$17.50/tablet
Viagra 100 mg tablet
$19.45/tablet
Viagra 25 mg tablet
$19.45/tablet
Viagra 50 mg tablet
$19.45/tablet
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
5 active patents, 4 expired
11337979
United States
Approved 24 May 2022 · Expires 24 Dec 2038
12y 8m
11464778
United States
Approved 11 Oct 2022 · Expires 24 Dec 2038
12y 8m
11759468
United States
Approved 19 Sept 2023 · Expires 24 Dec 2038
12y 8m
12005062
United States
Approved 11 Jun 2024 · Expires 24 Dec 2038
12y 8m
12186321
United States
Approved 24 Dec 2018 · Expires 24 Dec 2038
12y 8m
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated 27 days ago(8 Mar 2026)