Physiologically based pharmacokinetic modeling of drug–drug interactions between ritonavir‐boosted atazanavir and rifampicin in pregnancy

Autor: Shakir Atoyebi, Maiara Camotti Montanha, Ritah Nakijoba, Catherine Orrell, Henry Mugerwa, Marco Siccardi, Paolo Denti, Catriona Waitt
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: CPT: Pharmacometrics & Systems Pharmacology, Vol 13, Iss 11, Pp 1967-1977 (2024)
Druh dokumentu: article
ISSN: 2163-8306
DOI: 10.1002/psp4.13268
Popis: 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) for Ctrough and AUC0‐24 of both drugs were
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