Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Pregnant South African Women with Tuberculosis and HIV

Author:

Abdelwahab Mahmoud Tareq1ORCID,Leisegang Rory12,Dooley Kelly E.3,Mathad Jyoti S.4,Wiesner Lubbe1ORCID,McIlleron Helen1,Martinson Neil35,Waja Ziyaad5,Letutu Matebogo5,Chaisson Richard E.3,Denti Paolo1ORCID

Affiliation:

1. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

2. FAM-CRU, Stellenbosch University, Cape Town, South Africa

3. Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

4. Weill Cornell Medicine, Center for Global Health, New York, New York, USA

5. Perinatal HIV Research Unit (PHRU), Johannesburg, South Africa

Abstract

Tuberculosis is an important cause of maternal morbidity, but little is known about the effects of pregnancy on antituberculosis drug concentrations. We developed population pharmacokinetic models to describe drug dispositions of isoniazid, pyrazinamide, and ethambutol in pregnant women with tuberculosis and HIV. HIV-positive pregnant women with tuberculosis receiving standard first-line tuberculosis treatment and participating in Tshepiso, a prospective cohort study in Soweto, South Africa, underwent sparse pharmacokinetic sampling at >36 weeks of gestation and 7 weeks postpartum.

Funder

Swedish Foundation for International Cooperation in Research and Higher Education (STINT) jointly with South African National Research Council Foundation

HHS | National Institutes of Health

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | Fogarty International Center

National Research Foundation

Wellcome Trust

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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