Physiologically based pharmacokinetic modeling of drug-drug interactions between ritonavir-boosted atazanavir and rifampicin in pregnancy.

ABSTRACT: Ritonavir-boosted atazanavir (ATV/r) and rifampicin are mainstays of second-line antiretroviral and multiple anti-TB regimens, respectively. Rifampicin induces CYP3A4, a major enzyme involved in atazanavir metabolism, causing a drug-drug interaction (DDI) which might be exaggerated in pregnancy. Having demonstrated that increasing the dose of ATV/r from once daily (OD) to twice daily (BD) in non-pregnant adults can safely overcome this DDI, we developed a pregnancy physiologically based pharmacokinetic (PBPK) model to explore the impact of pregnancy. Predicted pharmacokinetic parameters were validated with separate clinical datasets of ATV/r alone (NCT03923231) and rifampicin alone in pregnant women. The pregnancy model was considered validated when the absolute average fold error (AAFE) f

SUBMITTER: Atoyebi S 

PROVIDER: S-EPMC11578135 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature