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Clin Pharmacol Ther. 2007 Nov;82(5):579-85. Epub 2007 Apr 18.

Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects.

Author information

1
Division of Clinical Pharmacology, Department of Medicine, Indiana University, School of Medicine, Indianapolis, Indiana, USA.

Erratum in

  • Clin Pharmacol Ther. 2010 Jul;88(1):138. Phillips, S [corrected to Philips, S].

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.

PMID:
17443134
DOI:
10.1038/sj.clpt.6100208
[Indexed for MEDLINE]

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