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Am J Perinatol 2013; 30(04): 275-282
DOI: 10.1055/s-0032-1323590
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Nifedipine Pharmacokinetics Are Influenced by CYP3A5 Genotype When Used as a Preterm Labor Tocolytic

David M. Haas
1   Department of Obstetrics and Gynecology Indiana University School of Medicine, Indianapolis
,
Sara K. Quinney
1   Department of Obstetrics and Gynecology Indiana University School of Medicine, Indianapolis
,
Jayanti M. Clay
1   Department of Obstetrics and Gynecology Indiana University School of Medicine, Indianapolis
,
Jamie L. Renbarger
2   Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis
,
Mary F. Hebert
3   Departments of Pharmacy and Obstetrics and Gynecology, University of Washington, Seattle, Washington
,
Shannon Clark
4   Division of MFM, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
,
Jason G. Umans
5   Center for Clinical and Translational Science, Georgetown-Howard Universities, Washington, District of Columbia
6   Medstar Health Research Institute, Hyattsville, Maryland
,
Steve N. Caritis
7   Division of MFM, Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
for the Obstetric-Fetal Pharmacology Research Units Network › Author Affiliations
Further Information

Publication History

26 March 2012

20 April 2012

Publication Date:
08 August 2012 (online)

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Abstract

Objective To characterize the pharmacokinetics and pharmacogenetics of nifedipine in pregnancy.

Study Design Pregnant women receiving oral nifedipine underwent steady-state pharmacokinetic testing over one dosing interval. DNA was obtained and genotyped for cytochrome P450 (CYP) 3A5 and CYP3A4*1B. Nifedipine and oxidized nifedipine concentrations were measured in plasma, and pharmacokinetic parameters were compared between those women who expressed a CYP3A5*1 allele and those who expressed only variant CYP3A5 alleles (*3,*6, or *7).

Results Fourteen women had complete data to analyze. Four women (29%) expressed variant CYP3A5; three of these women were also CYP3A4*1B allele carriers. The mean half-life of nifedipine was 1.68 ± 1.56 hours. The area under the curve from 0 to 6 hours for the women receiving nifedipine every 6 hours was 207 ± 138 µg·h /L. Oral clearance was different between high expressers and low expressers (232.0 ± 37.8 µg/mL versus 85.6 ± 45.0 µg/mL, respectively; p = 0.007).

Conclusion CYP3A5 genotype influences the oral clearance of nifedipine in pregnant women.

Keywords

nifedipine - pharmacokinetics - pharmacogenetics - pregnancy - tocolysis
 

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