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

David M. Haas, Sara K. Quinney, Jayanti M. Clay, Jamie L. 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 (US)
Pages (from-to)275-282
Number of pages8
JournalAmerican Journal of Perinatology
Volume30
Issue number4
DOIs
StatePublished - 2013

Fingerprint

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

Haas, D. M., Quinney, S. K., Clay, J. M., Renbarger, J. L., Hebert, M. F., Clark, S., ... Caritis, S. N. (2013). Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a preterm labor tocolytic. American Journal of Perinatology, 30(4), 275-282. https://doi.org/10.1055/s-0032-1323590

Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a preterm labor tocolytic. / Haas, David M.; Quinney, Sara K.; Clay, Jayanti M.; Renbarger, Jamie L.; 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, DM, Quinney, SK, Clay, JM, Renbarger, JL, Hebert, MF, Clark, S, Umans, JG & Caritis, SN 2013, 'Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a preterm labor tocolytic', American Journal of Perinatology, vol. 30, no. 4, pp. 275-282. https://doi.org/10.1055/s-0032-1323590
Haas, David M. ; Quinney, Sara K. ; Clay, Jayanti M. ; Renbarger, Jamie L. ; 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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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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