Drug Metabolism Letters - Volume 14, Issue 1, 2021

Background: CYP450 enzymes in the liver have a significant role in the metabolism of xenobiotics. Probe drug strategy is broadly used to evaluate the pharmacodynamic and pharmacokinetic drug/ herb-drug interactions/ food-drug interactions. Probe drugs reveal the exact pathway of drug metabolism in the liver by their targeted tractability property. The CYP3A4 isoenzyme metabolizes the majority of the drugs (65%). Meth Read More

Background: In healthy volunteers, the probe drug method is widely practised to assess the pharmacokinetic mediated herb-drug interactions (HDI). We analyzed the clinical evidence of CYP3 A4 probe drug, Midazolam. Methods: Literatures, where Midazolam was used as a probe drug for prediction of herb-drug interaction, were surveyed through an online database such as google scholar, Scopus, Cochrane, PubMed and Read More

Background: Saini et al. recently investigated the pharmacokinetics of darolutamide and its diastereomers in vitro and in vivo in Balb/c mice, reporting higher levels of (S,S)-darolutamide than (S,R)-darolutamide following intravenous or oral dosing, and interconversion of (S,R)-darolutamide to (S,S)-darolutamide. Objective: To present our in vitro and in vivo studies of darolutamide pharmacokinetics in mice, whi Read More

Background: Cytochrome P450 (CYP) contributes to a huge collection of medicinal products' Phase I metabolization. We aimed to summarize and investigate the current evidence regarding the frequency of CYP2D6, CYP2C9, CYP2C19, and MDR1 in Saudi Arabia. Methods: A computerized search in four databases was done using the relevant keywords. The screening process was done in two steps; title and abstract screeni Read More

Background: In order to avoid drug-induced liver injury (DILI), in vitro assays, which enable the assessment of both metabolic activation and immune reaction processes that ultimately result in DILI, are needed. Objective: In this study, recent progress in the application of in vitro assays using cell culture systems is reviewed for potential DILI-causing drugs/xenobiotics and a mechanistic study on DILI, as well as on the limit Read More

Background: Carbon-carbon bond cleavage of a saturated aliphatic moiety is rarely seen in xenobiotic metabolism. Olanexidine (Olanedine®), containing an n-octyl (C8) side chain, was mainly metabolized to various shortened side chain (C4 to C6) acid-containing metabolites in vivo in preclinical species. In liver microsomes and S9, the major metabolites of olanexidine were from multi-oxidation on its n-octyl (C8) side c Read More

Background: Darolutamide is recently approved for the treatment of non-metastatic castrate resistance prostate cancer. Hitherto, no stereoselective pharmacokinetic data have been published pertaining to darolutamide and its diastereomers in animals or humans. The key aims of the experiment were to examine darolutamide, S,S-darolutamide and S,R-darolutamide with respect to (a) assessment of in vitro metab Read More

Background: Ezetimibe is a cholesterol-lowering agent with an oral bioavailability of 50% by virtue of its poor solubility and extensive hepatic and intestinal metabolism. Objective: The study aimed to overcome low bioavailability issues of ezetimibe by formulating an oral disintegrating film. Methods: The low solubility of ezetimibe was undertaken, preparing solid dispersions using mannitol, β-cyclodextrin, and urea. The mann Read More

Objective: Previous studies have shown that catabolism of adenosine 5’-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity. We compared the acute toxicity of high doses of doxorubicin (DOX) and isoproterenol (ISO) on hemodynamics and ATP catabolism in the systemic circulation. Methods: sprague Dawley (SD) rats (n = 8 - 11) were each given either a single dose of 30 mg/kg Read More

Background: Food-drug interactions may lead to suppression or induction of drug metabolizing enzymes. Pomegranate is a commonly used fruit in folk medicine all over the world. Data concerning the effect of pomegranate on the activity of UDP-glucuronosyltransferases (UGTs) is scarce. Objective: The purpose of this work was to investigate the effect of pomegranate juice ingestion on the transcription of ugt2b1, ugt2a3, Read More