Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women

作者：Jyoti S. Mathad, Rada Savic, Paula Britto, Priya Jayachandran, Lubbe Wiesner, Grace Montepiedra, Jennifer Norman, Nan Zhang, Ellen Townley, Nahida Chakhtoura, Sarah Bradford, Sandesh Patil, Stephanie Popson, Tsungai Chipato, Vanessa Rouzier, Deborah Langat, Amphan Chalermchockcharoentkit, Portia Kamthunzi, Amita Gupta, Kelly E. Dooley · 发表于：Clinical Infectious Diseases · 年份：2021 · DOI：10.1093/cid/ciab665 · 被引用次数：34 · 研究领域：Tuberculosis Research and Epidemiology、Diagnosis and treatment of tuberculosis、Pregnancy and Medication Impact

BACKGROUND: Pregnancy increases the risk of tuberculosis and its complications. A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV, but 3HP has not been evaluated in pregnancy. METHODS: IMPAACT 2001 was a phase I/II trial evaluating the pharmacokinetics and safety of 3HP among pregnant women with indications for tuberculosis preventative therapy in Haiti, Kenya, Malawi, Thailand, and Zimbabwe (NCT02651259). Isoniazid and rifapentine were provided at standard doses (900 mg/week). Pharmacokinetic sampling was performed with the first (second/third trimester) and twelfth (third trimester/postpartum) doses. Nonlinear mixed-effects models were used to estimate drug population pharmacokinetics. RESULTS: Of 50 participants, 20 had HIV and were taking efavirenz-based antiretroviral therapy. Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum (1.20 vs 1.53 L/hour, P < .001), with area under the concentration-time curve (AUCSS) of 786 and 673 mg × hour/L, respectively. In pregnant women with HIV, clearance was 30% higher than women without HIV (P < .001), resulting in lower AUCss (522 mg × hour/L); clearance did not change significantly between pregnancy and postpartum. Pregnancy did not impact isoniazid pharmacokinetics. There were no drug-related serious adverse events, treatment discontinuations, or tuberculosis cases in women or in...