Population Pharmacokinetics of Bictegravir During Pregnancy and Postpartum: Role of Adherence in Maintaining Therapeutic Exposure

作者：Steven A Sun, Mina Nikanjam, Mark Mirochnick, Kathleen M. Powis, Ahizechukwu C. Eke, Alice Stek, Priyanka Arora, Tim R. Cressey, Kristina M. Brooks, Brookie M. Best, E. Capparelli, Jeremiah D. Momper · 发表于：The Journal of Clinical Pharmacology · 年份：2025 · DOI：10.1002/jcph.70134 · 被引用次数：1 · 研究领域：HIV/AIDS drug development and treatment、HIV/AIDS Research and Interventions、HIV-related health complications and treatments

Bictegravir is an integrase strand transfer inhibitor available in fixed-dose combination with emtricitabine and tenofovir alafenamide for HIV treatment. The objectives of this study were to develop a population pharmacokinetic model for bictegravir during pregnancy and postpartum, identify main drivers of between-subject variability, and evaluate the role of adherence patterns in maintaining therapeutic exposure. Intensive bictegravir concentration-time data were used from IMPAACT 2026, a pharmacokinetic study of selected antiretroviral drugs during pregnancy and postpartum. Five hundred and eight bictegravir plasma concentrations from 27 participants during the second and third trimesters of pregnancy and postpartum were utilized for model development. A one-compartment structural model best described bictegravir PK. Pregnancy increased bictegravir apparent clearance (CL/F) by 61% compared to postpartum, while Black/African American race was associated with a 32% increase in apparent volume of distribution (Vd/F). Plasma albumin concentrations were associated with a 43% decrease in CL/F and body weight was associated with a 120% increase in Vd/F over the range of observed values. Monte Carlo simulations predicted median (90% prediction interval) pre-dose bictegravir concentrations of 920 ng/mL (265-2081) during the third trimester and 3399 ng/mL (1423-6391) postpartum, exceeding the protein-adjusted 95% effective concentration (162 ng/mL). Adherence simulations predicted a ...