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drug-resistant TB regimens, but the recommended dose is not evidence based. Pharmacokinetic data from relevant patient populations are needed to inform dose optimization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine clofazimine exposure, evaluate covariate effects on variability, and simulate exposures for different dosing strategies in South African TB patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>Clinical and pharmacokinetic data were obtained from participants with pulmonary TB enrolled in two studies with intensive and sparse sampling for up to 6\u2009months. Plasma concentrations were measured by LC-MS\/MS and interpreted with non-linear mixed-effects modelling. Body size descriptors and other potential covariates were tested on pharmacokinetic parameters. We simulated different dosing regimens to safely shorten time to average daily concentration above a putative target concentration of 0.25\u2009mg\/L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We analysed 1570 clofazimine concentrations from 139 participants; 79 (57%) had drug-resistant TB and 54 (39%) were HIV infected. Clofazimine pharmacokinetics were well characterized by a three-compartment model. Clearance was 11.5\u2009L\/h and peripheral volume 10\u2009500\u2009L for a typical participant. Lower plasma exposures were observed in women during the first few months of treatment, explained by higher body fat fraction. Model-based simulations estimated that a loading dose of 200\u2009mg daily for 2\u2009weeks would achieve average daily concentrations above a target efficacy concentration 37\u2009days earlier in a typical TB participant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clofazimine was widely distributed with a long elimination half-life. Disposition was strongly influenced by body fat content, with potential dosing implications for women with TB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaa310","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T15:15:30Z","timestamp":1593011730000},"page":"3269-3277","source":"Crossref","is-referenced-by-count":71,"title":["Clofazimine pharmacokinetics in patients with TB: dosing implications"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-8749","authenticated-orcid":false,"given":"Mahmoud Tareq","family":"Abdelwahab","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South 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