Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a preterm labor tocolytic.

CONCLUSION: CYP3A5 genotype influences the oral clearance of nifedipine in pregnant women. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

OBJECTIVE: To characterize the pharmacokinetics and pharmacogenetics of nifedipine in pregnancy.

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 g.h /L. Oral clearance was different between high expressers and low expressers (232.0 +/- 37.8 g/mL versus 85.6 +/- 45.0 g/mL, respectively; p = 0.007).

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).

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