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

David Haas, Sara Quinney, Jayanti M. Clay, Jamie Renbarger, Mary F. Hebert, Shannon Clark, Jason G. Umans, Steve N. Caritis

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)275-282
Number of pages8
JournalAmerican Journal of Perinatology
Volume30
Issue number4
DOIs
StatePublished - 2013

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Tocolytic Agents
Cytochrome P-450 CYP3A
Premature Obstetric Labor
Nifedipine
Pharmacokinetics
Genotype
Alleles
Pregnant Women
Pharmacogenetics
Area Under Curve
Half-Life
Pregnancy
DNA

Keywords

  • nifedipine
  • pharmacogenetics
  • pharmacokinetics
  • pregnancy
  • tocolysis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a preterm labor tocolytic. / Haas, David; Quinney, Sara; Clay, Jayanti M.; Renbarger, Jamie; Hebert, Mary F.; Clark, Shannon; Umans, Jason G.; Caritis, Steve N.

In: American Journal of Perinatology, Vol. 30, No. 4, 2013, p. 275-282.

Research output: Contribution to journalArticle

Haas, David ; Quinney, Sara ; Clay, Jayanti M. ; Renbarger, Jamie ; Hebert, Mary F. ; Clark, Shannon ; Umans, Jason G. ; Caritis, Steve N. / Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a preterm labor tocolytic. In: American Journal of Perinatology. 2013 ; Vol. 30, No. 4. pp. 275-282.
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AU - Clark, Shannon

AU - Umans, Jason G.

AU - Caritis, Steve N.

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N2 - 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.

AB - 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.

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