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The International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s was a multicenter, phase IV, observational, prospective PK and safety study of antiretroviral and antituberculosis drugs administered as part of clinical care in pregnant persons living with and without HIV. We assessed the effects of pregnancy on rifampin, isoniazid, ethambutol, and pyrazinamide PK in pregnant and postpartum (PP) persons without HIV treated for drug-susceptible tuberculosis disease. Daily antituberculosis treatment was prescribed following World Health Organization-recommended weight-band dosing guidelines. Steady-state 12-hour PK profiles of rifampin, isoniazid, ethambutol, and pyrazinamide were performed during second trimester (2T), third trimester (3T), and 2\u20138 of weeks PP. PK parameters were characterized using noncompartmental analysis, and comparisons were made using geometric mean ratios (GMRs) with 90% confidence intervals (CI). Twenty-seven participants were included: 11 African, 9 Asian, 3 Hispanic, and 4 mixed descent. PK data were available for 17, 21, and 14 participants in 2T, 3T, and PP, respectively. Rifampin and pyrazinamide AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            and\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            in pregnancy were comparable to PP with the GMR between 0.80 and 1.25. Compared to PP, isoniazid AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            was 25% lower and\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            was 23% lower in 3T. Ethambutol AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            was 39% lower in 3T but limited by a low PP sample size. In summary, isoniazid and ethambutol concentrations were lower during pregnancy compared to PP concentrations, while rifampin and pyrazinamide concentrations were similar. However, the median AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            for rifampin, isoniazid, and pyrazinamide met the therapeutic targets. The clinical impact of lower isoniazid and ethambutol exposure during pregnancy needs to be determined.\n          <\/jats:p>","DOI":"10.1128\/aac.00737-23","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T13:00:50Z","timestamp":1698325250000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacokinetics and safety of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum: results from IMPAACT P1026s"],"prefix":"10.1128","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-901X","authenticated-orcid":true,"given":"Marije","family":"Van Schalkwyk","sequence":"first","affiliation":[{"name":"Division of Adult Infectious Diseases, Department of Medicine, Family Centre for Research with Ubuntu, Stellenbosch University and Tygerberg Hospital , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrie","family":"Bekker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Family Centre for Research with Ubuntu, Stellenbosch University and Tygerberg Hospital , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Decloedt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Stellenbosch University and Tygerberg Hospital , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard B.","family":"Theron","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Stellenbosch University , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark F.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Family Centre for Research with Ubuntu, Stellenbosch University and Tygerberg Hospital , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahizechukwu C.","family":"Eke","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine and Clinical Pharmacology, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine , Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim R.","family":"Cressey","sequence":"additional","affiliation":[{"name":"AMS-PHPT Research Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Bacon","sequence":"additional","affiliation":[{"name":"Frontier Science Foundation , Amherst, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Knowles","sequence":"additional","affiliation":[{"name":"Frontier Science Foundation , Amherst, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"George","sequence":"additional","affiliation":[{"name":"FHI 360 , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Browning","sequence":"additional","affiliation":[{"name":"Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahida","family":"Chakhtoura","sequence":"additional","affiliation":[{"name":"Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittipong","family":"Rungruengthanakit","sequence":"additional","affiliation":[{"name":"Research Institute for Health Sciences, Chiang Mai University , Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-8699","authenticated-orcid":true,"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"}]},{"given":"Edmund V.","family":"Capparelli","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California , San Diego, California, USA"},{"name":"Department of Pediatrics, School of Medicine, University of California , San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Stek","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Southern California School of Medicine , Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mirochnick","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Boston University Chobanian &amp; Avedisian School of Medicine , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brookie M.","family":"Best","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California , San Diego, California, USA"},{"name":"Department of Pediatrics, School of Medicine, University of California , San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the IMPAACT P1026s Protocol Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"World Health Organization\n. 2022. 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