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Pharmacogenetics of pregnancy‐induced changes in efavirenz pharmacokinetics
Author(s) -
Olagunju A,
Bolaji O,
Amara A,
Else L,
Okafor O,
Adejuyigbe E,
Oyigboja J,
Back D,
Khoo S,
Owen A
Publication year - 2015
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.43
Subject(s) - cmin , cmax , pharmacokinetics , efavirenz , cyp2b6 , pregnancy , medicine , pharmacogenetics , pharmacology , bioequivalence , obstetrics , genotype , cyp3a4 , chemistry , biology , human immunodeficiency virus (hiv) , immunology , cytochrome p450 , biochemistry , gene , genetics , metabolism , antiretroviral therapy , viral load
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) C min was 1,000 ng/mL (429–5,190) with no significant change in C max ( P = 0.072). However, when stratified for CYP2B6 516G>T (rs3745274) genotype, efavirenz AUC 0‐24 , C max and C min 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.