Pharmacokinetics of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum with and without efavirenz-based antiretroviral treatment: IMPAACT P1026s study.

The pharmacokinetics (PK) of antituberculosis drugs may be altered by both pregnancy-induced physiological changes and drug interactions in individuals living with HIV who develop tuberculosis. Within the multicenter International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s study, we assessed the PK of rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum (PP) in women on efavirenz-based antiretroviral therapy (ART). Results were compared to a previously published non-HIV group and described minimum targets. World Health Organization-recommended daily doses of antituberculosis and ART medications were administered, followed by PK sampling of all antituberculosis drugs over 24 h during the second trimester (2T), third trimester (3T), and 2-8 weeks PP. PK parameters were characterized using noncompartmental analysis, and comparisons were made among stages of pregnancy and between groups using geometric mean ratios with 90% confidence intervals. Twenty-two participants were enrolled, and PK data were available for 12, 20, and 13 participants in 2T, 3T, and PP, respectively. While no significant difference in rifampin exposure between pregnancy and postpartum was detected, the median area-under-the-plasma-concentration-time-curve up to 24 h post-dose (AUC