Valproic acid 250mg/5ml oral solution
Requires a prescription from a doctor or prescriber
Valproic acid, or valproate, is an fatty acid derivative and anticonvulsant originally synthesized in 1881 by Beverly S.
Safety information for pregnancy and breastfeeding
Pregnancy
Reproductive Toxicity
Valproate use in pregnancy is known to increase the risk of neural tube defects and other structural abnormalities.[FDA Label] The risk of spina bifida increases from 0.06-0.07% in the normal population to 1-2% in valproate users.
Pregnancy Registry reports a major malformation rate of 9-11%, 5 times the baseline rate.
Lactation
Valproate is excreted in human milk.[FDA Label] Data in the published literature describe the presence of valproate in human milk (range: 0.4 mcg/mL to 3.9 mcg/mL), corresponding to 1% to 10% of maternal serum levels.
Breastfeeding
Lactation
Valproate is excreted in human milk.[FDA Label] Data in the published literature describe the presence of valproate in human milk (range: 0.4 mcg/mL to 3.9 mcg/mL), corresponding to 1% to 10% of maternal serum levels.
via breast milk.
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
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Official medicine documents
Safety monitoring data
Yellow Card reports
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.
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Suspected adverse reactions reported for Valproic acid
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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
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.
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Suspected adverse reactions reported for Valproic acid
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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
WHO defined daily dose (DDD)
1.5 gram
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
Therapeutically similar medicines
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.
NHS prescribing volume and spending trends
Clinical guidelines and formulary information
British National Formulary
Valproic acid
Source: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(4)
Bipolar disorder: assessment and management (CG185)
Antenatal and postnatal mental health (QS115)
Antenatal and postnatal mental health: clinical management and service guidance (CG192)
Fremanezumab for preventing migraine (TA764)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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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
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
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
29 found
Half-life
13-19 hours
Mechanism
The exact mechanisms by which valproate exerts it's effects on epilepsy, migrain…
Food interactions
3 warnings
Human targets
16 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
4 hours
Half-life
13-19 hours
The half-life in neonates ranges from 10-67 hours while the half-life in pediatric patients under 2 months of age ranges from 7-13 hours.…
Protein binding
10%
Volume of distribution
11 L
Metabolism
30-50%
Elimination
30-50%
Clearance
0.56 L/h
Pediatric patients between 3 months and 10 years of age have 50% higher clearances by weight.…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Since then, it has been investigated for neuroprotective, anti-manic, and anti-migraine effects. It is currently a compound of interest in the field of oncology for its anti-proliferative effects and is the subject of many clinical trials in a variety of cancer types.
1) Use as monotherapy or adjunctive therapy in the management of complex partial seizures and simple or complex absence seizures.
2) Adjunctive therapy in the management of multiple seizure types that include absence seizures.
3) Prophylaxis of migraine headaches.
4) Acute management of mania associated with bipolar disorder.
Off-label uses include:
1) Maintenance therapy for bipolar disorder.
[A177919]
2) Treatment for acute bipolar depression.
[A177928][A177931][A177934]
3) Emergency treatment of status epilepticus.
[A177955]
Known interactions with other medications. Always consult a healthcare professional.
Showing 50 of 1734 interactions
Oral, mouse: 1098 mg/kg
Oral, rat: 670 mg/kg
Overdose
Symptoms of overdose include somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported, however patients have recovered from valproate serum concentrations as high as 2120 mcg/mL. The unbound fraction may be removed by hemodialysis.
Naloxone has been demonstrated to reverse the CNS depressant effects of overdose but may also reverse the anti-epileptic effects.[FDA Label]
Reproductive Toxicity
Valproate use in pregnancy is known to increase the risk of neural tube defects and other structural abnormalities.[FDA Label] The risk of spina bifida increases from 0.06-0.07% in the normal population to 1-2% in valproate users. The North American Antiepileptic Drug (NAAED)
Pregnancy Registry reports a major malformation rate of 9-11%, 5 times the baseline rate. These malformations include neural tube defects, cardiovascular malformations, craniofacial defects (e.g., oral clefts, craniosynostosis), hypospadias, limb malformations (e.g., clubfoot, polydactyly), and other malformations of varying severity involving other body systems.
Other antiepileptic drugs, lamotrigine, carbemazepine, and phenytoin, have been found to reduce IQ in children exposed in utero. Valproate was also studied however the results did not achieve statistical significance (97 IQ (CI: 94-101)). Observational studies report an absolute risk increase of 2.9% (relative risk 2.9 times baseline) of autism spectrum disorder in children exposed to valproate in utero.
There have been case reports of fatal hepatic failure in children of mothers who used valproate during pregnancy.
There have been reports of male infertility when taking valproate.[FDA Label]
Lactation
Valproate is excreted in human milk.[FDA Label] Data in the published literature describe the presence of valproate in human milk (range: 0.4 mcg/mL to 3.9 mcg/mL), corresponding to 1% to 10% of maternal serum levels. Valproate serum concentrations collected from breastfed infants aged 3 days postnatal to 12 weeks following delivery ranged from 0.7 mcg/mL to 4 mcg/mL, which were 1% to 6% of maternal serum valproate levels. A published study in children up to six years of age did not report adverse developmental or cognitive effects following exposure to valproate
via breast milk.
Other Toxicity Considerations
Use in pediatrics under 2 years of age increases the risk of fatal hepatotoxicity.[FDA Label]
Valproate is known to inhibit succinic semialdehyde dehydrogenase.[A177991] This inhibition results in an increase in succinic semialdehyde which acts as an inhibitor of GABA transaminase ultimately reducing GABA metabolism and increasing GABAergic neurotransmission. As GABA is an inhibitory neurotransmitter, this increase results in increased inhibitory activity.[A457] A possible secondary contributor to cortical inhibition is a direct suppression of voltage gated sodium channel activity and indirect suppression through effects on GABA.
It has also been suggested that valproate impacts the extracellular signal-related kinase pathway (ERK).[A457] These effects appear to be dependent on mitogen-activated protein kinase (MEK) and result in the phosphorylation of ERK1/2. This activation increases expression of several downstream targets including ELK-1 with subsequent increases in c-fos, growth cone-associated protein-43 which contributes to neural plasticity, B-cell lymphoma/leukaemia-2 which is an anti-apoptotic protein, and brain-derived neurotrophic factor (BDNF) which is also involved in neural plasticity and growth. Increased neurogenesis and neurite growth due to valproate are attributed to the effects of this pathway. An additional downstream effect of increased BDNF expression appears to be an increase in GABAA receptors which contribute further to increased GABAergic activity.[A177997]
Valproate exerts a non-competitive indirect inhibitory effect on myo-inosital-1-phophate synthetase.[A178000] This results in reduced de novo synthesis of inositol monophosphatase and subsequent inositol depletion. It is unknown how this contributed to valproate's effects on bipolar disorder but [lithium] is known to exert a similar inositol-depleting effect.[A178003] Valproate exposure also appears to produce down-regulation of protein kinase C proteins (PKC)-α and -ε which are potentially related to bipolar disorder as PKC is unregulated in the frontal cortex of bipolar patients. This is further supported by a similar reduction in PKC with lithium.[A178015] The inhibition of the PKC pathway may also be a contributor to migraine prophylaxis.[A178018] Myristoylated alanine-rich C kinase substrate, a PKC substrate, is also downregulated by valproate and may contribute to changes in synaptic remodeling through effects on the cytoskeleton.[A178021]
Valproate also appears to impact fatty acid metabolism.[A457] Less incorporation of fatty acid substrates in sterols and glycerolipids is thought to impact membrane fluidity and result in increased action potential threshold potentially contributing to valproate's antiepileptic action.[A178024] Valproate has been found to be a non-competitive direct inhibitor of brain microsomal long-chain fatty acyl-CoA synthetase.[A14708] Inhibition of this enzyme decreases available arichidonyl-CoA, a substrate in the production of inflammatory prostaglandins. It is thought that this may be a mechanism behind valproate's efficacy in migraine prophylaxis as migraines are routinely treated with non-steroidal anti-inflammatory drugs which also inhibit prostaglandin production.
Finally, valproate acts as a direct histone deactylase (HDAC) inhibitor.[A178030] Hyperacetylation of lysine residues on histones promoted DNA relaxation and allows for increased gene transcription. The scope of valproate's genomic effects is wide with 461 genes being up or down-regulated.[A178027] The relation of these genomic effects to therapeutic value is not fully characterized however H3 and H4 hyperacetylation correlates with improvement of symptoms in bipolar patients.[A178033] Histone hyperacetylation at the BDNF gene, increasing BDNF expression, post-seizure is known to occur and is thought to be a neuroprotective mechanism which valproate may strengthen or prolong.[A178036] H3 hyperacetylation is associated with a reduction in glyceraldehyde-3-phosphate dehydrogenase, a pro-apoptotic enzyme, contributing further to valproate's neuroprotective effects.[A11814]
Valproate is hepatotoxic and teratogenic. The reasons for this are unclear but have been attributed to the genomic effects of the drug.[A457]
A small proof-of concept study found that valproate increases clearance of human immunodeficiency virus (HIV) when combined with highly active antiretroviral therapy (HAART) by reactivating the virus to allow clearance, however, a larger multicentre trial failed to show a significant effect on HIV reservoirs when added to HAART.[A458][A177859] The FDA labeling contains a warning regarding HIV reactivation during valproate use.[label].
How the body processes this drug — absorption, distribution, metabolism, and elimination
[L6196]
The extended release tablet formulation had Tmax increase from 4 hours to 8 hours when taken with food.
In comparison, the sprinkle capsule formulation had Tmax increase from 3.3 hours to 4.8 hours. Bioavailability is reported to be approximately 90% with all oral formulations with enteric-coated forms possibly reaching 100%.
[A178066]
The half-life in neonates ranges from 10-67 hours while the half-life in pediatric patients under 2 months of age ranges from 7-13 hours.
[A178066]
Binding is expected to decrease in the elderly and patients with hepatic dysfunction.
Pediatric patients between 3 months and 10 years of age have 50% higher clearances by weight. Pediatric patients 10 years of age or older approximate adult values.[FDA Label]
Proteins and enzymes this drug interacts with in the body
PMID:11749387 PMID:17478001 PMID:19366350
Requires primed phosphorylation of the majority of its substrates .
PMID:11749387 PMID:17478001 PMID:19366350
Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis .
PMID:11749387 PMID:17478001 PMID:19366350
Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors .
PMID:10868943 PMID:17478001
In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin .
PMID:17229088
Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease .
PMID:12761548
May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity).
Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions which activates KAT5/TIP60 acetyltransferase activity and promotes acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer .
PMID:30704899
Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B.
The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR PMID:25897075
PMID:10407778 PMID:15528998
Can also convert delta-aminovalerate and beta-alanine (By similarity)
PMID:10832746 PMID:11013134 PMID:21430231 PMID:7698750
Among the different mitochondrial acyl-CoA dehydrogenases, acts specifically on short and branched chain acyl-CoA derivatives such as (S)-2-methylbutyryl-CoA as well as short straight chain acyl-CoAs such as butyryl-CoA .
PMID:10832746 PMID:11013134 PMID:21430231 PMID:7698750
Plays an important role in the metabolism of L-isoleucine by catalyzing the dehydrogenation of 2-methylbutyryl-CoA, one of the steps of the L-isoleucine catabolic pathway .
PMID:10832746 PMID:11013134
Can also act on valproyl-CoA, a metabolite of valproic acid, an antiepileptic drug PMID:8660691
PMID:24495017 PMID:25210035 PMID:28435050
Participates in the first step, rate limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) catalyzed by the whole OGDHC .
PMID:24495017 PMID:25210035 PMID:28435050
Catalyzes the irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST) .
PMID:24495017 PMID:25210035 PMID:28435050 PMID:35272141
Plays a key role in the Krebs (citric acid) cycle, which is a common pathway for oxidation of fuel molecules, including carbohydrates, fatty acids, and amino acids .
PMID:25210035
Can catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much lower rate than 2-oxoglutarate .
PMID:28435050
Mainly active in the mitochondrion .
PMID:29211711
A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A PMID:29211711
Enzymes involved in drug metabolism — important for understanding drug interactions
Proteins that transport this drug across cell membranes
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
PMID:10454528 PMID:10525100 PMID:10966938 PMID:17509700 PMID:20722056 PMID:33124720
Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium.
Relative uptake activity ratio of carnitine to TEA is 11.3 .
PMID:10454528 PMID:10525100 PMID:10966938
In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from B.subtilis which induces cytoprotective heat shock proteins contributing to intestinal homeostasis .
PMID:18005709
May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
PMID:12946269 PMID:32946811 PMID:33333023
Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH .
PMID:12946269 PMID:33333023
The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (By similarity).
Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart .
PMID:32946811
Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition PMID:33333023
PMID:11327718 PMID:18216183 PMID:21446918 PMID:28945155
Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively .
PMID:11327718 PMID:25904762
Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates .
PMID:11327718 PMID:18216183 PMID:26377792 PMID:28945155
Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways .
PMID:18216183 PMID:26377792
Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood .
PMID:21446918
Involved in renal secretion and possible reabsorption of creatinine .
PMID:25904762 PMID:28945155
Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate .
PMID:11327718 PMID:26377792
Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified PMID:26377792
PMID:10873595 PMID:11159893 PMID:11932330 PMID:12724351 PMID:14610227 PMID:16908597 PMID:18501590 PMID:20507927 PMID:22201122 PMID:23531488 PMID:25132355 PMID:26383540 PMID:27576593 PMID:28408210 PMID:29871943 PMID:34628357
Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) .
PMID:11932330 PMID:12409283
Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver .
PMID:11159893
Mediates the intestinal uptake of sulfated steroids .
PMID:12724351 PMID:28408210
Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain .
PMID:16908597 PMID:25132355
Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC .
PMID:35714613
Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition .
PMID:26383540
Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity 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:14610227 PMID:19129463 PMID:22201122
The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound .
PMID:19129463 PMID:20507927 PMID:26277985
Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions .
PMID:19129463
Cytoplasmic glutamate may also act as counteranion in the placenta .
PMID:26277985
An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) PMID:20507927
Proteins that carry this drug through the body
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
ATC N03AG01
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)
Valproic acid
Additional database identifiers
Drugs Product Database (DPD)
2115
ChemSpider
3009
BindingDB
50003616
PDB
2PP
ZINC
ZINC000003008621
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14065
GenAtlas
HDAC9
GeneCards
HDAC9
GenBank Gene Database
AY032737
GenBank Protein Database
15590680
Guide to Pharmacology
2620
UniProt Accession
HDAC9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4616
GeneCards
GSK3A
Guide to Pharmacology
2029
UniProt Accession
GSK3A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:23
GenAtlas
ABAT
GeneCards
ABAT
GenBank Gene Database
L32961
GenBank Protein Database
602705
Guide to Pharmacology
2464
UniProt Accession
GABT_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:91
GenAtlas
ACADSB
GeneCards
ACADSB
GenBank Gene Database
U12778
GenBank Protein Database
531391
UniProt Accession
ACDSB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8124
GenAtlas
OGDH
GeneCards
OGDH
GenBank Gene Database
D10523
GenBank Protein Database
531241
UniProt Accession
ODO1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:408
GenAtlas
ALDH5A1
GeneCards
ALDH5A1
GenBank Gene Database
Y11192
GenBank Protein Database
3766467
Guide to Pharmacology
2466
UniProt Accession
SSDH_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10585
GenAtlas
SCN1A
GeneCards
SCN1A
GenBank Gene Database
AF225985
GenBank Protein Database
12642270
Guide to Pharmacology
578
UniProt Accession
SCN1A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10582
GenAtlas
SCN10A
GeneCards
SCN10A
GenBank Gene Database
AF117907
GenBank Protein Database
4838145
Guide to Pharmacology
585
UniProt Accession
SCNAA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10583
GenAtlas
SCN11A
GeneCards
SCN11A
GenBank Gene Database
AF188679
GenBank Protein Database
6572950
UniProt Accession
SCNBA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10588
GenAtlas
SCN2A
GeneCards
SCN2A
GenBank Gene Database
M94055
GenBank Protein Database
457879
Guide to Pharmacology
579
UniProt Accession
SCN2A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10590
GenAtlas
SCN3A
GeneCards
SCN3A
GenBank Gene Database
AJ251507
GenBank Protein Database
7414320
Guide to Pharmacology
580
UniProt Accession
SCN3A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10591
GenAtlas
SCN4A
GeneCards
SCN4A
GenBank Gene Database
M81758
GenBank Protein Database
338213
Guide to Pharmacology
581
UniProt Accession
SCN4A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10593
GenAtlas
SCN5A
GeneCards
SCN5A
GenBank Gene Database
M77235
GenBank Protein Database
184039
Guide to Pharmacology
582
UniProt Accession
SCN5A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10594
GeneCards
SCN7A
UniProt Accession
SCN7A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10596
GenAtlas
SCN8A
GeneCards
SCN8A
GenBank Gene Database
AF050736
GenBank Protein Database
4321647
Guide to Pharmacology
583
UniProt Accession
SCN8A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10597
GenAtlas
SCN9A
GeneCards
SCN9A
GenBank Gene Database
X82835
GenBank Protein Database
758110
Guide to Pharmacology
584
UniProt Accession
SCN9A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10586
GeneCards
SCN1B
GenBank Gene Database
L10338
GenBank Protein Database
307415
UniProt Accession
SCN1B_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10589
GeneCards
SCN2B
GenBank Gene Database
AF007783
GenBank Protein Database
3309111
UniProt Accession
SCN2B_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:20665
GeneCards
SCN3B
GenBank Gene Database
AJ243396
GenBank Protein Database
7160975
UniProt Accession
SCN3B_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10592
GeneCards
SCN4B
GenBank Gene Database
AY149967
GenBank Protein Database
27465047
UniProt Accession
SCN4B_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4853
GenAtlas
HDAC2
GeneCards
HDAC2
GenBank Gene Database
U31814
GenBank Protein Database
1667394
Guide to Pharmacology
2616
UniProt Accession
HDAC2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9232
GenAtlas
PPARA
GeneCards
PPARA
GenBank Gene Database
L02932
GenBank Protein Database
307341
Guide to Pharmacology
593
UniProt Accession
PPARA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9235
GenAtlas
PPARD
GeneCards
PPARD
GenBank Gene Database
L07592
GenBank Protein Database
190230
Guide to Pharmacology
594
UniProt Accession
PPARD_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9236
GenAtlas
PPARG
GeneCards
PPARG
GenBank Gene Database
U79012
GenBank Protein Database
1711117
Guide to Pharmacology
595
UniProt Accession
PPARG_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4852
GenAtlas
HDAC1
GeneCards
HDAC1
GenBank Gene Database
U50079
GenBank Protein Database
1277084
Guide to Pharmacology
2658
UniProt Accession
HDAC1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:19086
GeneCards
HDAC11
Guide to Pharmacology
2615
UniProt Accession
HDA11_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4853
GenAtlas
HDAC2
GeneCards
HDAC2
GenBank Gene Database
U31814
GenBank Protein Database
1667394
Guide to Pharmacology
2616
UniProt Accession
HDAC2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4854
GenAtlas
HDAC3
GeneCards
HDAC3
GenBank Gene Database
U66914
GenBank Protein Database
2326173
Guide to Pharmacology
2617
UniProt Accession
HDAC3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14063
GenAtlas
HDAC4
GeneCards
HDAC4
GenBank Gene Database
AF132607
Guide to Pharmacology
2659
UniProt Accession
HDAC4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14068
GenAtlas
HDAC5
GeneCards
HDAC5
GenBank Gene Database
BK000028
Guide to Pharmacology
2660
UniProt Accession
HDAC5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14067
GenAtlas
HDAC7
GeneCards
HDAC7
GenBank Gene Database
BC020505
Guide to Pharmacology
2661
UniProt Accession
HDAC7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:13315
GenAtlas
HDAC8
GeneCards
HDAC8
GenBank Gene Database
AF230097
GenBank Protein Database
8118721
Guide to Pharmacology
2619
UniProt Accession
HDAC8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14065
GenAtlas
HDAC9
GeneCards
HDAC9
GenBank Gene Database
AY032737
GenBank Protein Database
15590680
Guide to Pharmacology
2620
UniProt Accession
HDAC9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:18128
GenAtlas
HDAC10
GeneCards
HDAC10
GenBank Gene Database
AL512711
Guide to Pharmacology
2614
UniProt Accession
HDA10_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14064
GenAtlas
HDAC6
GeneCards
HDAC6
GenBank Gene Database
AF132609
GenBank Protein Database
4754911
Guide to Pharmacology
2618
UniProt Accession
HDAC6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1784
GeneCards
CDKN1A
UniProt Accession
CDN1A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4893
GenAtlas
HGF
GeneCards
HGF
GenBank Gene Database
M29145
GenBank Protein Database
306846
UniProt Accession
HGF_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:2610
GenAtlas
CYP2A6
GeneCards
CYP2A6
GenBank Gene Database
X13897
Guide to Pharmacology
1321
UniProt Accession
CP2A6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_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: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:9604
GenAtlas
PTGS1
GeneCards
PTGS1
GenBank Gene Database
M31822
GenBank Protein Database
387018
Guide to Pharmacology
1375
UniProt Accession
PGH1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2596
GenAtlas
CYP1A2
GeneCards
CYP1A2
GenBank Gene Database
Z00036
Guide to Pharmacology
1319
UniProt Accession
CP1A2_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:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12536
GeneCards
UGT1A4
GenBank Gene Database
M57951
GenBank Protein Database
184475
UniProt Accession
UD14_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12540
GeneCards
UGT1A8
GenBank Gene Database
AF030310
GenBank Protein Database
2613044
UniProt Accession
UD18_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12531
GeneCards
UGT1A10
GenBank Gene Database
U89508
GenBank Protein Database
2039362
UniProt Accession
UD110_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12538
GeneCards
UGT1A6
UniProt Accession
UD16_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12535
GeneCards
UGT1A3
GenBank Gene Database
M84127
GenBank Protein Database
340135
UniProt Accession
UD13_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12554
GeneCards
UGT2B7
GenBank Gene Database
J05428
GenBank Protein Database
340080
UniProt Accession
UD2B7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12546
GeneCards
UGT2B15
UniProt Accession
UDB15_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12541
GeneCards
UGT1A9
GenBank Gene Database
S55985
GenBank Protein Database
7690346
UniProt Accession
UD19_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12530
GeneCards
UGT1A1
GenBank Gene Database
M57899
GenBank Protein Database
184473
Guide to Pharmacology
2990
UniProt Accession
UD11_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10970
GenAtlas
hROAT1
GeneCards
SLC22A6
GenBank Gene Database
AF057039
GenBank Protein Database
3831566
Guide to Pharmacology
1025
UniProt Accession
S22A6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10972
GeneCards
SLC22A8
GenBank Gene Database
AF097491
GenBank Protein Database
4378059
Guide to Pharmacology
1027
UniProt Accession
S22A8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10969
GenAtlas
SLC22A5
GeneCards
SLC22A5
GenBank Gene Database
AF057164
GenBank Protein Database
3273741
UniProt Accession
S22A5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10922
GenAtlas
SLC16A1
GeneCards
SLC16A1
GenBank Gene Database
L31801
GenBank Protein Database
561722
Guide to Pharmacology
988
UniProt Accession
MOT1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10971
GeneCards
SLC22A7
GenBank Gene Database
AF097518
GenBank Protein Database
5001689
UniProt Accession
S22A7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10962
GenAtlas
SLCO2B1
GeneCards
SLCO2B1
GenBank Gene Database
AB026256
GenBank Protein Database
5006263
Guide to Pharmacology
1224
UniProt Accession
SO2B1_HUMAN
International reference pricing
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
All patents expired, 6 expired
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: