A pilot study of the impact of genotype on nifedipine pharmacokinetics when used as a tocolytic
David M Haas1, Sara K Quinney, Catherine L McCormick
1Department of Obstetrics & Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA. dahaas@iupui.edu
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.
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