Pharmacogenetics of pregnancy-induced changes in efavirenz pharmacokinetics

Clin Pharmacol Ther. 2015 Mar;97(3):298-306. doi: 10.1002/cpt.43. Epub 2015 Jan 20.

Abstract

Pregnancy-induced physiological changes alter many drugs' pharmacokinetics. We investigated pregnancy-induced changes in efavirenz pharmacokinetics in 25 pregnant and 19 different postpartum women stratified from 211 HIV-positive women in whom a preliminary pharmacogenetic study had been undertaken. Despite significant changes in CL/F during pregnancy (42.6% increase; P = 0.023), median (range) Cmin was 1,000 ng/mL (429-5,190) with no significant change in Cmax (P = 0.072). However, when stratified for CYP2B6 516G>T (rs3745274) genotype, efavirenz AUC0-24 , Cmax and Cmin were 50.6% (P = 0.0013), 17.2% (P = 0.14), and 61.6% (P = 0.0027) lower during pregnancy (n = 8) compared with postpartum (n = 6) in 516G homozygotes, with values of 25,900 ng.h/mL (21,700-32,600), 2,640 ng/mL (1,260-3,490), and 592 ng/mL (429-917), respectively, and CL/F was 100% higher (P = 0.0013). No changes were apparent in CYP2B6 516 heterozygotes (14 pregnant vs. 7 postpartum). The clinical implications of these findings warrant further investigation.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Alkynes
  • Anti-HIV Agents / pharmacokinetics
  • Benzoxazines / pharmacokinetics*
  • Case-Control Studies
  • Cyclopropanes
  • Cytochrome P-450 CYP2A6 / genetics
  • Cytochrome P-450 CYP2B6 / genetics*
  • Female
  • Homozygote
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Postpartum Period / genetics*
  • Pregnancy
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Receptors, Cytoplasmic and Nuclear
  • constitutive androstane receptor
  • CYP2A6 protein, human
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 CYP2B6
  • efavirenz