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

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 CYP3A41B. Nifedipine and oxidized nifedipine concentrations were measured in plasma, and pharmacokinetic parameters were compared between those women who expressed a CYP3A51 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.