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

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.

Keywords:

• Nifedipine
• pharmacogenetics
• pharmacokinetics
• preterm labor

Acknowledgements

This work was supported by a grant from the Berlex Scholar Award in Clinical Research (Haas), a Research Support Funds Grant from Indiana University–Purdue University Indianapolis (Haas), and an IUPUI Signature Center Grant to PREGMED, the Indiana University Center for Pharmacogenetics and Therapeutics Research in Maternal and Child Health.

Declaration of interest:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.