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

MedStar author(s):
Citation: American Journal of Perinatology. 30(4):275-81, 2013 Apr.PMID: 22875663Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Comparative Study | Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Cytochrome P-450 CYP3A/ge [Genetics] | *Nifedipine/pk [Pharmacokinetics] | *Obstetric Labor, Premature/pc [Prevention & Control] | *Polymorphism, Genetic | *Tocolytic Agents/pk [Pharmacokinetics] | Adolescent | Adult | Alleles | Cohort Studies | Dose-Response Relationship, Drug | Female | Gene Expression Regulation | Genotype | Humans | Infant, Newborn | Nifedipine/ad [Administration & Dosage] | Obstetric Labor, Premature/ge [Genetics] | Pharmacogenetics | Pregnancy | Pregnancy Outcome | Prospective Studies | Statistics, Nonparametric | Tocolytic Agents/ad [Administration & Dosage] | Young AdultYear: 2013ISSN:
  • 0735-1631
Name of journal: American journal of perinatologyAbstract: 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).All authors: Caritis SN, Clark S, Clay JM, Haas DM, Hebert MF, Obstetric-Fetal Pharmacology Research Units Network, Quinney SK, Renbarger JL, Umans JGFiscal year: FY2013Digital Object Identifier: Date added to catalog: 2013-12-24
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Journal Article MedStar Authors Catalog Article 22875663 Available 22875663

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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