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

Y. Jin, Y. H. Wang, J. Miao, L. Li, R. J. Kovacs, R. Marunde, M. A. Hamman, S. Phillips, J. Hilligoss, S. D. Hall

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30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)579-585
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume82
Issue number5
DOIs
StatePublished - Nov 2007

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Jin, Y., Wang, Y. H., Miao, J., Li, L., Kovacs, R. J., Marunde, R., Hamman, M. A., Phillips, S., Hilligoss, J., & Hall, S. D. (2007). Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects. Clinical Pharmacology and Therapeutics, 82(5), 579-585. https://doi.org/10.1038/sj.clpt.6100208