{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:55:38Z","timestamp":1792065338991,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>IMPAACT 2001 (NCT02651259) evaluated the safety and pharmacokinetics (PK) of once\u2010weekly 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\u2010to\u2010plasma ratio parameters were estimated. For mother\u2013infant pairs, maternal plasma PK was simulated for the last RPT dose pre\u2010delivery (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\u2010lives were 0.568\u2009hr and 0.439\u2009hr, 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 &lt;1%. Within 72\u2009hours 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.<\/jats:p>","DOI":"10.1002\/cpt.70479","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:25:16Z","timestamp":1792063516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of Rifapentine and Desacetyl Rifapentine in Maternal Plasma and Breast Milk &amp; Infant Cord Blood and Plasma: A Model\u2010Based Analysis of Mother\u2013Infant Pairs for Tuberculosis Prevention"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4197-4085","authenticated-orcid":false,"given":"Priya","family":"Jayachandran","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9487-7775","authenticated-orcid":false,"given":"Jyoti S.","family":"Mathad","sequence":"additional","affiliation":[{"name":"Department of Medicine and Obstetrics and Gynecology, Center for Global Health Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5031-9480","authenticated-orcid":false,"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5682-1403","authenticated-orcid":false,"given":"Paula","family":"Britto","sequence":"additional","affiliation":[{"name":"Harvard T. H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-8699","authenticated-orcid":false,"given":"Lubbe","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6866-4335","authenticated-orcid":false,"given":"Grace","family":"Montepiedra","sequence":"additional","affiliation":[{"name":"Harvard T. H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2017-0870","authenticated-orcid":false,"given":"Jennifer","family":"Norman","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3894-9996","authenticated-orcid":false,"given":"Ellen","family":"Townley","sequence":"additional","affiliation":[{"name":"Division of AIDS National Institute of Allergy and Infectious Diseases  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5199-5093","authenticated-orcid":false,"given":"Sarah","family":"Bradford","sequence":"additional","affiliation":[{"name":"FHI 360  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4007-0295","authenticated-orcid":false,"given":"Sandesh","family":"Patil","sequence":"additional","affiliation":[{"name":"BJ Medical College\u2013Johns Hopkins CTU  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4102-8346","authenticated-orcid":false,"given":"Stephanie","family":"Popson","sequence":"additional","affiliation":[{"name":"Frontier Science and Technology Research Foundation, Inc  Amherst New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3629-3429","authenticated-orcid":false,"given":"Tsungai","family":"Chipato","sequence":"additional","affiliation":[{"name":"University of Zimbabwe College of Health Sciences\u2013Clinical Trials Research Centre  Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-9474","authenticated-orcid":false,"given":"Vanessa","family":"Rouzier","sequence":"additional","affiliation":[{"name":"Department of Medicine and Obstetrics and Gynecology, Center for Global Health Weill Cornell Medicine  New York New York USA"},{"name":"Les Centres GHESKIO Clinical Research Site  Port\u2010au\u2010Prince Haiti"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0439-1099","authenticated-orcid":false,"given":"Deborah","family":"Langat","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\/Walter Reed Project Clinical Research Center  Kericho Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5776-6988","authenticated-orcid":false,"given":"Amphan","family":"Chalermchockcharoentkit","sequence":"additional","affiliation":[{"name":"Siriraj Hospital, Mahidol University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7036-2718","authenticated-orcid":false,"given":"Amita","family":"Gupta","sequence":"additional","affiliation":[{"name":"Frontier Science and Technology Research Foundation, Inc  Amherst New York USA"},{"name":"Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9013-5256","authenticated-orcid":false,"given":"Kelly E.","family":"Dooley","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3143-5579","authenticated-orcid":false,"given":"Radojka","family":"Savic","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the IMPAACT 2001 Study Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/pathogens11121481","article-title":"Tuberculosis infection in pregnant people: current practices and research priorities","volume":"11","author":"Mathad J.S.","year":"2022","journal-title":"Pathogens."},{"key":"e_1_2_10_2_1","volume-title":"Priftin (Rifapentine) [Package Insert]","author":"Sanofi Aventis"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1093\/cid\/cis732","article-title":"Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps","volume":"55","author":"Mathad J.S.","year":"2012","journal-title":"Clin. 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Ther."},{"key":"e_1_2_10_24_1","volume-title":"TB Knowledge Sharing Platform Operational Handbook","author":"World Health Organization"},{"key":"e_1_2_10_25_1","unstructured":"Salazar\u2010Austin N.et al.DOLPHIN\u2010KIDS: Phase I\/II Trial of Dolutegravir With 3HP for TB Prevention in Children With HIV (ABSTRACT 150)CROI; February 22\u201025 2026; Denver CO."},{"key":"e_1_2_10_26_1","unstructured":"Mathad J.S.et al.DOLPHIN Moms: Pharmacokinetics and HIV Suppression with Dolutegravir and 1HP or 3HP in PregnancyCROI; March 9\u201012 2025; San Francisco CA."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70479","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70479","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70479","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:25:25Z","timestamp":1792063525000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":26,"alternative-id":["10.1002\/cpt.70479"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70479","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"2026-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70479"}}