Pharmacokinetics of Rifapentine and Desacetyl Rifapentine in Maternal Plasma and Breast Milk & Infant Cord Blood and Plasma: A Model‐Based Analysis of Mother–Infant Pairs for Tuberculosis Prevention
Year: 2026
Type: article
Abstract: IMPAACT 2001 (NCT02651259) evaluated the safety and pharmacokinetics (PK) of once-weekly isoniazid and rifapentine in pregnant and postpartum women for tuberculosis prevention. Rifapentine (RPT) and desacetyl rifapentine (desRPT) PK data were collected in maternal plasma, breast milk, infant cord blood, and infant plasma. Longitudinal maternal plasma and breast milk RPT and desRPT concentrations were characterized using a multicompartment PK model with biophase effect compartments (NONMEM v7.4). Rate parameters describing drug entry into breast milk from plasma and breast milk-to-plasma ratio parameters were estimated. For mother-infant pairs, maternal plasma PK was simulated for the last RPT dose pre-delivery (with HIV and partum status covariates), and concentration ratios (observed infant cord blood or plasma relative to simulated maternal plasma) were calculated at the infant PK sample collection time. For RPT and desRPT, derived equilibration half-lives were 0.568 hr and 0.439 hr, and estimated concentration ratios of breast milk to maternal plasma were 0.0236 and 0.0411, respectively, indicating rapid equilibration between maternal plasma and breast milk and a minimal extent of drug excretion into breast milk. Maximum relative infant dose was estimated at <1%. Within 72 hours of maternal dosing, median concentration ratios of observed infant cord blood and plasma to predicted maternal plasma were approximately 0.280 and 0.612 for RPT and 0.493 and 1.83 for desRPT, respectively. RPT crosses the placenta and is measurable in infant plasma at concentrations unlikely to be clinically significant. Breast milk concentrations are very low, supporting safe use of RPT in breastfeeding women.
DOI: 10.1002/cpt.70479
Authors: Priya Jayachandran, Jyoti S. Mathad, Nan Zhang, Paula Britto, Lubbe Wiesner, Grace Montepiedra, Jennifer Norman, Ellen Townley, Sarah Bradford, Sandesh Patil, Stephanie Popson, Tsungai Chipato, Vanessa Rouzier, Deborah Langat, Amphan Chalermchockcharoentkit, Amita Gupta, Kelly E. Dooley, Radojka Savic, the IMPAACT 2001 Study Team
Institutions: University of California, San Francisco, Cornell University, Center for Global Health, Harvard University, University of Cape Town, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Family Health International 360, B. J. Medical College & Sassoon Hospital, Frontier Science & Technology Research Foundation, Inc., University of Zimbabwe, Gheskio Centers, United States Army Medical Research Directorate - Africa, Reed Medical (United Kingdom), Siriraj Hospital, Mahidol University, Johns Hopkins University, Vanderbilt University Medical Center
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,410
Funders: International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institutes of Health, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1100245349, G1654426238, G1857750563, G2384456196, G3045663399, G3262353703, G32641939, G3342746445, G3365999844, G3665517470, G454726209, G4853082081, G4927240118, G5602729146, G6585143688, G7093710796, G7184647664, G7445317512, G7502524018, G803170016, G8500352392, G8709470907, G876279366, G8922259349, G9000030691, G9000063086, G9000153711, G9000278504, SDMC - IMPAACT Leadership Group
OpenAlex ID: W7222120446