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

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

Research output: Contribution to journalArticle

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

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Cytochrome P-450 CYP3A
Verapamil
Healthy Volunteers
Genotype
Alleles
Pharmacokinetics
Pharmacology
Blood Pressure
Hypertension

ASJC Scopus subject areas

  • Pharmacology

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Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects. / Jin, Y.; Wang, Y. H.; Miao, J.; Li, L.; Kovacs, Richard; Marunde, R.; Hamman, M. A.; Phillips, S.; Hilligoss, J.; Hall, S. D.

In: Clinical Pharmacology and Therapeutics, Vol. 82, No. 5, 11.2007, p. 579-585.

Research output: Contribution to journalArticle

Jin, Y, Wang, YH, Miao, J, Li, L, Kovacs, R, Marunde, R, Hamman, MA, Phillips, S, Hilligoss, J & Hall, SD 2007, 'Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects', Clinical Pharmacology and Therapeutics, vol. 82, no. 5, pp. 579-585. https://doi.org/10.1038/sj.clpt.6100208
Jin, Y. ; Wang, Y. H. ; Miao, J. ; Li, L. ; Kovacs, Richard ; Marunde, R. ; Hamman, M. A. ; Phillips, S. ; Hilligoss, J. ; Hall, S. D. / Cytochrome P450 3A5 genotype is associated with verapamil response in healthy subjects. In: Clinical Pharmacology and Therapeutics. 2007 ; Vol. 82, No. 5. pp. 579-585.
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