A pilot study of the impact of genotype on nifedipine pharmacokinetics when used as a tocolytic

David M. Haas, Sara K. Quinney, Catherine L. McCormick, David R. Jones, Jamie L. Renbarger

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Objective.To characterize the pharmacokinetics of nifedipine when used for tocolysis in preterm labor and to determine the impact of genetics on these parameters. Study design.Pharmacokinetic study performed on women given tocolytic nifedipine. Over one dosing interval, drug concentrations, clinical data, and genotype for Cytochrome P450 (CYP)3A5 polymorphisms were obtained. Non-compartmental pharmacokinetic analysis was used to estimate nifedipine exposure at steady state. Results.The mean nifedipine area under the curve in 20 pregnant women was 86.1±61.1 ng/ml/h. The mean nifedipine exposure differed by expression of CYP3A5 (expressers [exp]: 139.5±97.3 ng/ml/h vs. nonexpressers[non]: 68.3 ± 31.8 ng/ml/h, p = 0.02). Four women consumed CYP3A inhibitors and this affected the nifedipine concentrations (p < 0.001). CYP3A5 expressers had less improvement in contraction frequency after the loading dose (p = 0.04), at steady state (p = 0.006), and at 0-1 h after the study dose (p < 0.001). Conclusions.CYP3A5 genotype plays a role in nifedipine concentration when used as a tocolytic.

Original languageEnglish (US)
Pages (from-to)419-423
Number of pages5
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume25
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Nifedipine
  • pharmacogenetics
  • pharmacokinetics
  • preterm labor

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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