title: Pharmacogenetics of pregnancy-induced changes in efavirenz pharmacokinetics.
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.
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK; Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
authors: A
authors: A
authors: Olagunju
authors: O
authors: O
authors: Bolaji
authors: A
authors: A
authors: Amara
authors: L
authors: L
authors: Else
authors: O
authors: O
authors: Okafor
authors: E
authors: E
authors: Adejuyigbe
authors: J
authors: J
authors: Oyigboja
authors: D
authors: D
authors: Back
authors: S
authors: S
authors: Khoo
authors: A
authors: A
authors: Owen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics; D048588:Benzoxazines / Q000493:pharmacokinetics*; D016022:Case-Control Studies; D000090702:Constitutive Androstane Receptor; D003521:Cyclopropanes; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049590:Postpartum Period / Q000235:genetics*; D011247:Pregnancy; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D000090702:Constitutive Androstane Receptor; D003521:Cyclopropanes; D018160:Receptors, Cytoplasmic and Nuclear; C585710:CYP2A6 protein, human; C585599:CYP2B6 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz