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- Title
Cytochrome P450 3A5 Genotype is Associated with Verapamil Response in Healthy Subjects.
- Authors
Jin, Y.; Wang, Y.-H.; Miao, J.; Li, L.; Kovacs, R. J.; Marunde, R.; Hamman, M. A.; Phillips, S.; Hilligoss, J.; Hall, S. D.
- Abstract
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.Clinical Pharmacology & Therapeutics (2007) 82, 579–585; doi:10.1038/sj.clpt.6100208; published online 18 April 2007
- Subjects
CARDIOVASCULAR agents; GENETIC polymorphisms; CLINICAL medicine; PHARMACODYNAMICS; CLINICAL pharmacology
- Publication
Clinical Pharmacology & Therapeutics, 2007, Vol 82, Issue 5, p579
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/sj.clpt.6100208