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

Academic Article

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.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Jin Y; Wang YH; Miao J; Li L; Kovacs RJ; Marunde R; Hamman MA; Phillips S; Hilligoss J; Hall SD
  • Start Page

  • 579
  • End Page

  • 585
  • Volume

  • 82
  • Issue

  • 5