Cytochrome P450 3A5 Genotype is Associated with Verapamil Response in Healthy Subjects
| Autor: | Y, Jin, Y-H, Wang, J, Miao, L, Li, R J, Kovacs, R, Marunde, M A, Hamman, S, Philips, S, Phillips, J, Hilligoss, S D, Hall |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype Metabolic Clearance Rate Vasodilator Agents medicine.medical_treatment Antiarrhythmic agent Pharmacology Electrocardiography Cytochrome P-450 Enzyme System Pharmacokinetics Heart Conduction System Reference Values Internal medicine Cytochrome P-450 CYP3A medicine Humans Pharmacology (medical) Prospective Studies CYP3A5 Polymorphism Genetic biology business.industry Cytochrome P450 Calcium Channel Blockers Isoenzymes Blood pressure Endocrinology Verapamil biology.protein Female business Anti-Arrhythmia Agents medicine.drug |
| Zdroj: | Clinical Pharmacology & Therapeutics. 82:579-585 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/sj.clpt.6100208 |
| Popis: | We hypothesized that CYP3A5 genotype contributes to the interindividual variability in verapamil response. Healthy subjects (n=26) with predetermined CYP3A5 genotypes were categorized as expressers (at least one CYP3A5(*)1 allele) and nonexpressers (subjects without a CYP3A5(*)1 allele). Verapamil pharmacokinetics and pharmacodynamics were determined after 7 days of dosing with 240 mg daily. There was a significantly higher oral clearance of R-verapamil (165.1+/-86.4 versus 91.2+/-36.5 l/h; P=0.009) and S-verapamil (919.4+/-517.4 versus 460.2+/-239.7 l/h; P=0.01) in CYP3A5 expressers compared to nonexpressers. Consequently, CYP3A5 expressers had significantly less PR-interval prolongation (19.5+/-12.3 versus 44.0+/-19.4 ms; P=0.0004), and had higher diastolic blood pressure (69.2+/-7.5 versus 61.6+/-5.1 mm Hg; P=0.036) than CYP3A5 nonexpressers after 7 days dosing with verapamil. CYP3A5 expressers display a greater steady-state oral clearance of verapamil and may therefore experience diminished pharmacological effect of verapamil due to a greater steady state oral clearance. |
| Databáze: | OpenAIRE |
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