RESEARCH ARTICLE A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV [version 1; peer review: awaiting peer review] Noha Abdelgawad 1 , Maxwell Chirehwa 1 , Charlotte Schutz 2,3 , David Barr 4 , Amy Ward 2,3 , Saskia Janssen 5 , Rosie Burton 3,6 , Robert J. Wilkinson 2,3,7,8 , Muki Shey 2 , Lubbe Wiesner 1 , Helen McIlleron 1,2 , Gary Maartens 1,2 , Graeme Meintjes 2,3 , Paolo Denti 1 1 Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, 7925, South Africa 2 Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925, South Africa 3 Department of Medicine, University of Cape Town, Observatory, 7925, South Africa 4 Wellcome Trust Liverpool Glasgow Centre for Global Health Research, University of Liverpool, Liverpool, L3 5QA, UK 5 Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, 19268, The Netherlands 6 Khayelitsha Hospital, Department of Medicine, Khayelitsha, 7784, South Africa 7 Department of Infectious Diseases, Imperial College London, London, W12 0NN, UK 8 The Francis Crick Institute, London, NW1 1AT, UK First published: 28 Feb 2022, 7:72 https://doi.org/10.12688/wellcomeopenres.17660.1 Latest published: 28 Feb 2022, 7:72 https://doi.org/10.12688/wellcomeopenres.17660.1 v1 Abstract Background. Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups. Methods. Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM ® was used to analyze the data. Results. Data from 60 hospitalized patients (11 of whom died within 12 weeks Open Peer Review Approval Status AWAITING PEER REVIEW Any reports and responses or comments on the article can be found at the end of the article. Page 1 of 13 Wellcome Open Research 2022, 7:72 Last updated: 28 FEB 2022