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Title: Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping
Authors: Kamunkhwala Gausi
Lubbe Wiesner
Jennifer Norman
Carole L. Wallis
Carolyne Onyango-Makumbi
Tsungai Chipato
David W. Haas
Renee Browning
Nahida Chakhtoura
Grace Montepiedra
Lisa Aaron
Katie McCarthy
Sarah Bradford
Tichaona Vhembo
Lynda Stranix-Chibanda
Gaerolwe R. Masheto
Avy Violari
Blandina T. Mmbaga
Linda Aurpibul
Ramesh Bhosale
Neetal Nevrekhar
Vanessa Rouzier
Enid Kabugho
Mercy Mutambanengwe
Vongai Chanaiwa
Mandisa Nyati
Tsungai Mhembere
Fuanglada Tongprasert
Anneke Hesseling
Katherine Shin
Bonnie Zimmer
Diane Costello
Patrick Jean-Philippe
Timothy R. Sterling
Gerhard Theron
Adriana Weinberg
Amita Gupta
Paolo Denti
Keywords: Medicine
Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2020
Abstract: © 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. The World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty-seven women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting for NAT2 and CYP2B6 genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in CYP2B6 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 NAT2 and CYP2B6 genotypes, which resulted in a five-fold difference for both drugs between rapid and slow metabolizers.
ISSN: 15326535
Appears in Collections:CMUL: Journal Articles

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