Linezolid Population Pharmacokinetics in South African Adults with Drug-Resistant Tuberculosis

Author:

Abdelwahab Mahmoud Tareq1ORCID,Wasserman Sean123ORCID,Brust James C. M.4,Dheda Keertan567ORCID,Wiesner Lubbe1ORCID,Gandhi Neel R.89,Warren Robin M.10,Sirgel Frederick A.10,Meintjes Graeme2,Maartens Gary12ORCID,Denti Paolo1ORCID

Affiliation:

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

2. Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

3. Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

4. Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, USA

5. Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute, Cape Town, South Africa

6. South African Medical Research Council Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa

7. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom

8. Departments of Epidemiology and Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA

9. Division of Infectious Diseases, Department of Medicine, Emory School of Medicine, Emory University, Atlanta, Georgia, USA

10. DST-NRF Centre of Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa

Abstract

Linezolid is widely used for drug-resistant tuberculosis (DR-TB) but has a narrow therapeutic index. To inform dose optimization, we aimed to characterize the population pharmacokinetics of linezolid in South African participants with DR-TB and explore the effect of covariates, including HIV coinfection, on drug exposure.

Funder

European and Developing Countries Clinical Trials Partnership

HHS | NIH | Fogarty International Center

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | National Institutes of Health

National Department of Health

National Research Foundation

Newcastle University | Wellcome Trust Centre for Mitochondrial Research

South African Medical Research Council

UKRI | Medical Research Council

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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