Ketoprofen 100mg / Omeprazole 20mg modified-release capsules

INTRODUCTION: Methotrexate (MTX) is an antifolate and immunosuppressive drug prescribed for various malignancies and immune diseases. However, delayed elimination of MTX associated with concomitant use of some medications can lead to severe and lifethreatening adverse effects. AREAS COVERED: This paper investigated drugMTX interactions that lead to elevated MTX levels and related adverse effects due to the role of transporters. Methotrexate toxicity occurs at both low and high doses administrations. According to the studies we reviewed in this paper, most interaction records with methotrexate occurred with coadministration of indomethacin, ketoprofen, omeprazole, piperacillin/tazobactam, ciprofloxacin, cotrimoxazole, probenecid, and imatinib, mainly due to the role of transporters. However, most studies were performed as case reports or series, and confirming the exact drugmethotrexate interaction still needs further clinical investigations. EXPERT OPINION: Our findings showed no firm evidence of interactions of proton pump inhibitors (PPIs), levetiracetam, and NSAIDS with MTX. Moreover, patients' risk factors, hypoalbuminemia, renal failure, third space fluid retention, the elderly, polypharmacy, and transport inhibition are the most critical factors for MTX toxicity. If substitution or temporary discontinuation is not possible, healthcare providers should be aware of interactions, especially in patients with risk factors for MTX toxicity.

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The increasing incidence of erythromycin and erythromycin-induced resistance to clindamycin among Staphylococcus aureus (S. aureus) is a serious problem. Patients infected with inducible resistance phenotypes may fail to respond to clindamycin. This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.

Abstract licence: CC BY

When developing an amorphous solid dispersion (ASD), a prudent choice of polymer is critical to several aspects of ASD performance including: processability, solid state stability and dissolution rate. However, there is little guidance available to formulators to aid judicious polymer selection and a "trial and error" approach is often taken. This study aims to facilitate rational polymer selection and formulation design by generating ASDs using a range of poly-vinyl polymers and ketoprofen as a model active pharmaceutical ingredient (API) and evaluating several aspects of their performance. The molecular weight of the polymer and the ratio of vinyl pyrrolidone to vinyl acetate in the polymer were found to influence the relative humidity at which the relative humidity induced glass transition occurred, as well as the extent of ketoprofen supersaturation achieved during dynamic solubility testing. Interestingly, ASD tablets containing polymers with the vinyl pyrrolidone functional group exhibited higher tensile strengths than those without. This points towards the binder functionality of vinyl pyrrolidone. In conclusion, the physicochemical properties of poly-vinyl polymers greatly influence ketoprofen ASD performance and due regard should be paid to these properties in order to develop an ASD with the desired attributes.

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Omeprazole, a proton pump inhibitor used to treat peptic ulcer and gastroesophageal reflux disease, has been associated to chronic kidney disease and acute interstitial nephritis. However, whether omeprazole is toxic to renal cells is unknown. Omeprazole has a lethal effect over some cancer cells, and cell death is a key process in kidney disease. Thus, we evaluated the potential lethal effect of omeprazole over tubular cells. Omeprazole induced dose-dependent cell death in human and murine proximal tubular cell lines and in human primary proximal tubular cell cultures. Increased cell death was observed at the high concentrations used in cancer cell studies and also at lower concentrations similar to those in peptic ulcer patient serum. Cell death induced by omeprazole had features of necrosis such as annexin V/7-AAD staining, LDH release, vacuolization and irregular chromatin condensation. Weak activation of caspase-3 was observed but inhibitors of caspases (zVAD), necroptosis (Necrostatin-1) or ferroptosis (Ferrostatin-1) did not prevent omeprazole-induced death. However, omeprazole promoted a strong oxidative stress response affecting mitochondria and lysosomes and the antioxidant N-acetyl-cysteine reduced oxidative stress and cell death. By contrast, iron overload increased cell death. An adaptive increase in the antiapoptotic protein BclxL failed to protect cells. In mice, parenteral omeprazole increased tubular cell death and the expression of NGAL and HO-1, markers of renal injury and oxidative stress, respectively. In conclusion, omeprazole nephrotoxicity may be related to induction of oxidative stress and renal tubular cell death.

Abstract licence: CC BY-NC-ND

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of the potential impurities of dexketoprofen, including the distomer R-ketoprofen. After screening the separation capability of four polysaccharide columns (Lux Amylose-1, Lux Amylose-2, Lux Cellulose-1 and Lux Cellulose-2) in polar organic and in reversed-phase modes, appropriate enantioseparation was observed only on the Lux Amylose-2 column in an acidified acetonitrile/water mixture. A detailed investigation of the mobile phase composition and temperature for enantio- and chemoselectivity showed many unexpected observations. It was observed that both the resolution and the enantiomer elution order can be fine-tuned by varying the temperature and mobile phase composition. Moreover, hysteresis of the retention times and enantioselectivity was also observed in reversed-phase mode using methanol/water mixtures on amylose-type columns. This could indicate that the three-dimensional structure of the amylose column can change by transitioning from a polar organic to a reversed-phase mode, which affects the enantioseparation process. Temperature-dependent enantiomer elution order and rare enthalpic/entropic controlled enantioseparation in the operative temperature range were also observed in reversed-phase mode. To find the best methodological conditions for the determination of dexketoprofen impurities, a full factorial optimization design was performed. Using the optimized parameters (Lux Amylose-2 column with water/acetonitrile/acetic acid 50/50/0.1 (v/v/v) at a 1 mL/min flow rate at 20 °C), baseline separations were achieved between all compounds within 15 min. Our newly developed HPLC method was validated according to the current guidelines, and its application was tested on commercially available pharmaceutical formulations. According to the authors’ knowledge, this is the first study to report hysteretic behavior on polysaccharide columns in reversed-phase mode.

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Introduction: Non-steroidal anti-inflammatory medicines (NSAIDs) help to lower inflammation and pain, but improper prescription can cause potential drug-drug interactions (pDDIs), affecting the therapeutic outcomes. Given the great frequency of polypharmacy and concomitant medication interactions, NSAID-related problems are especially pertinent in outpatient settings. This study aims to assess the prescription pattern of NSAIDs at the Outpatient Pharmacy Department of a Secondary Care Hospital in the Northern Emirates of the United Arab Emirates. Methods: A prospective observational study based on data from electronic medical records of patients who received NSAID prescriptions from Jan-June 2023. Data collected were screened for prescription patterns of NSAIDs and polypharmacy, and the potential drug-drug interactions (pDDIs) were identified using the Portable Emergency Physician Information Database (PEPID). Data were extracted and analyzed using descriptive statistics and logistic regression analysis to study the association between treatment-related variables and the presence of pDDIs. Chi-square was used to test the association between the type of NSAID prescribed and co-prescribed gastro-protective agents. P < 0.05 was considered statistically significant. Results: In total, 1005 NSAID prescriptions were analyzed, with a majority (53.23%) being prescribed to female patients. Pain related to elbow/shoulder/joints/lower back (41.09%) was the most common diagnosis in the study populations. Celecoxib (49.7%) was the most commonly prescribed oral, and Ketoprofen (39.5%) was the predominant topical NSAID. A significant association was found between the prescribed NSAID and its co-prescription with gastroprotective agents, specifically ibuprofen, celecoxib, piroxicam, meloxicam (P < 0.001), diclofenac (P = 0.007), and aspirin (P = 0.001). Age and chronic illnesses such as diabetes mellitus (OR = 1.446; 95% CI: 1.018-2.054) and cardiovascular disease (OR = 1.818; 95% CI: 1.279-2.585) are significantly associated with polypharmacy. Multiple logistic regression analysis revealed that the pDDIs were significantly higher with an increasing number of prescribed drugs and co-morbidities (p < 0.001). Conclusion: The study examines NSAID prescribing trends and emphasizes the potential for drug-related issues, particularly in light of polypharmacy, which calls for careful monitoring and prescribing practices. Healthcare providers should routinely conduct medication reviews and team up with clinical pharmacists to ensure rational NSAID use, reduce drug interactions, and enhance patient safety by thus mitigating this risks.

Abstract licence: CC BY

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered in all age groups due to their effectiveness in reducing fever, relieving pain, and reducing inflammation. However, they have also been identified as the second most common cause of drug-induced hypersensitivity reactions, after beta-lactam antibiotics. Adverse reactions to NSAIDs can range from expected pharmacological side effects such as gastritis to severe allergies, including anaphylaxis. It is important to distinguish true hypersensitivity reactions from other side effects to ensure proper management and patient safety. Four patients aged 35-60 years were treated with NSAIDs for pain management and subsequently developed hypersensitivity reactions to NSAIDs such as ketorolac, ketoprofen, and diclofenac sodium in the type of allergic reactions such as NSAIDs-induced urticaria/angioedema (NIUA). This case series provides valuable insights into the clinical presentations and potential mechanisms of NSAID hypersensitivity in the documented cases in one of the hospitals in Indonesia. It highlights important areas for future investigation, including the need for larger, controlled studies to better understand incidence, risk factors, and generalizability to broader populations.

Abstract licence: CC BY-NC