title: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  CYP3A5 genotype influences the oral clearance of nifedipine in pregnant women.
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA. dahaas@iupui.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Haas
authors.forename: Sara K
authors.initials: SK
authors.lastname: Quinney
authors.forename: Jayanti M
authors.initials: JM
authors.lastname: Clay
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Renbarger
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.forename: Shannon
authors.initials: S
authors.lastname: Clark
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009543:Nifedipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007752:Obstetric Labor, Premature / Q000235:genetics / Q000517:prevention & control*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D015149:Tocolytic Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D009543:Nifedipine