Premium
Alteration in cytochrome P 450 3 A 4 activity as measured by a urine cortisol assay in HIV ‐1‐infected pregnant women and relationship to antiretroviral pharmacokinetics
Author(s) -
Aweeka FT,
Hu C,
Huang L,
Best BM,
Stek A,
Lizak P,
Burchett SK,
Read JS,
Watts H,
Mirochnick M,
Capparelli EV
Publication year - 2015
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12195
Subject(s) - medicine , pharmacokinetics , cyp3a , confidence interval , pregnancy , postpartum period , lopinavir , cyp3a4 , urine , area under the curve , obstetrics , urinary system , gastroenterology , endocrinology , physiology , viral load , immunology , human immunodeficiency virus (hiv) , antiretroviral therapy , cytochrome p450 , metabolism , biology , genetics
Objectives Pregnancy results in physiological changes altering the pharmacokinetics of drugs metabolized by cytochrome P 450 3 A 4 ( CYP3A4 ). The urinary ratio of 6‐β hydroxycortisol to cortisol ( 6βHF : F ) is a marker of CYP3A4 induction. We sought to evaluate its change in antiretroviral ( ARV )‐treated HIV ‐1‐infected women and to relate this change to ARV pharmacokinetics. Methods Women receiving various ARVs had pharmacokinetic evaluations during the third trimester of pregnancy (> 30 weeks) and postpartum with determination of 6β HF : F carried out on the same days. The W ilcoxon signed rank test was used to compare the ratio antepartum to postpartum. The relationship between the change in ratio and the change in pharmacokinetics was analysed using K endall's tau. Results 6βHF : F ratios were available for 107 women antepartum, with 54 having postpartum values. The ratio was higher antepartum ( P = 0.033) (median comparison 1.35; 95% confidence interval 1.01, 1.81). For 71 women taking a protease inhibitor (PI), the antepartum vs. postpartum 6β HF : F comparison was marginally significant ( P = 0.058). When the change in the 6β HF : F ratio was related to the change in the dose‐adjusted ARV area under the plasma concentration vs. time curve ( AUC ) between antepartum and postpartum, the 35 subjects in the lopinavir/ritonavir ( LPV /r) arms demonstrated an inverse relationship ( P = 0.125), albeit this correlation did not reach statistical significance. Conclusions A 35% increase in the urinary 6β HF : F ratio was measured during late pregnancy compared with postpartum, indicating that CYP3A induction occurs during pregnancy. The trend towards an inverse relationship between the change in the 6β HF : F ratio and the change in the LPV AUC antepartum vs. postpartum suggests that CYP3A induction may be one mechanism behind altered LPV exposure during pregnancy.