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We investigated pregnancy\u2010induced and pharmacogenetic\u2010associated pharmacokinetic changes and drug\u2010drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty\u2010seven women received isoniazid for 28\u00a0weeks, either during pregnancy or at 12\u00a0weeks postpartum, and 786 women received efavirenz. After adjusting for <jats:italic>NAT2<\/jats:italic> and <jats:italic>CYP2B6<\/jats:italic> genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in <jats:italic>CYP2B6<\/jats:italic> normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration were <jats:italic>NAT2<\/jats:italic> and <jats:italic>CYP2B6<\/jats:italic> genotypes, which resulted in a five\u2010fold difference for both drugs between rapid and slow metabolizers.<\/jats:p>","DOI":"10.1002\/cpt.2044","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T20:39:55Z","timestamp":1600288795000},"page":"1034-1044","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Pharmacokinetics and Drug\u2010Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9002-8087","authenticated-orcid":false,"given":"Kamunkhwala","family":"Gausi","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Department of Medicine University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":"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"}]},{"given":"Carole L.","family":"Wallis","sequence":"additional","affiliation":[{"name":"BARC Laboratories South Africa Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyne","family":"Onyango\u2010Makumbi","sequence":"additional","affiliation":[{"name":"Makerere University \u2013 Johns Hopkins University Research Collaboration Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsungai","family":"Chipato","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Zimbabwe College of Health Sciences Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Haas","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Pharmacology, Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine Nashville Tennessee USA"},{"name":"Department of Internal Medicine Meharry Medical College Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Browning","sequence":"additional","affiliation":[{"name":"Division of AIDS National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahida","family":"Chakhtoura","sequence":"additional","affiliation":[{"name":"National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Montepiedra","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research Harvard T. 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