학술논문
Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women
Document Type
article
Author
Mathad, Jyoti S; Savic, Rada; Britto, Paula; Jayachandran, Priya; Wiesner, Lubbe; Montepiedra, Grace; Norman, Jennifer; Zhang, Nan; Townley, Ellen; Chakhtoura, Nahida; Bradford, Sarah; Patil, Sandesh; Popson, Stephanie; Chipato, Tsungai; Rouzier, Vanessa; Langat, Deborah; Chalermchockcharoentkit, Amphan; Kamthunzi, Portia; Gupta, Amita; Dooley, Kelly E
Source
Clinical Infectious Diseases. 74(9)
Subject
Language
Abstract
BackgroundPregnancy 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.MethodsIMPAACT 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.ResultsOf 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