The genetic test is gradually replacing probe drugs as the primary tool for screening populations for the CYP2C19 polymorphism. A full appreciation for the clinical and toxicological relevance of this genetic variation is presently limited. Further research is needed in several areas. The development and use of 3-D models of the CYP2C19 enzyme to automate and increase the rate at which CYP2C19 substrates are identified could reap great benefits. Meanwhile, clinical research should begin to determine whether the CYP2C19 polymorphism affects therapeutic outcomes and toxicity of drugs in actual patient settings. Combining research efforts in molecular modeling, genetic testing, clinical and epidemiological research will be required if better appreciation of this genetic variation and its importance in the population at large is to emerge.
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http://dx.doi.org/10.1159/000028398 | DOI Listing |
Pharmaceuticals (Basel)
January 2025
Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand.
: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP).
View Article and Find Full Text PDFFront Pharmacol
January 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Introduction: Deglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM.
Methods: A combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile.
J Clin Pharmacol
January 2025
Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
Obesity significantly influences drug pharmacokinetics (PK), which challenges optimal dosing. This study examines the effects of diet-and-exercise-induced weight loss on key drug-metabolizing enzymes and gastric emptying in patients with obesity, who frequently require medications for comorbidities. Participants followed a structured weight management program promoting weight loss over 3-6 months and were not concomitantly on potential CYP inducers or inhibitors.
View Article and Find Full Text PDFClin Pract Epidemiol Ment Health
December 2024
Laboratory of Panic and Respiration, Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro (UFRJ). Rio de Janeiro, RJ, Brazil.
Background: Many pharmacological treatments are considered effective in the treatment of panic disorder (PD), however, about 20 to 40% of the patients have treatment-resistant PD. Pharmacogenetics could explain why some patients are treatment-resistant.
Objective: Our objective was to gather preliminary data on the clinical usefulness of pharmacogenetic testing in this disorder.
Eur J Clin Pharmacol
January 2025
Electrical and Computer Engineering Department, School of Engineering, Lebanese American University, P.O. Box: 36, Byblos, F-19, Lebanon.
Objective: The study aims to verify the usage of mathematical modeling in predicting patients' medication doses in association with their genotypes versus real-world data.
Methods: The work relied on collecting, extracting, and using real-world data on dosing and patients' genotypes. Drug metabolizing enzymes, i.
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