{"doi":"10.1093/jac/dkaa310","title":"Clofazimine pharmacokinetics in patients with TB: dosing implications","abstract":"BACKGROUND: Clofazimine is in widespread use as a key component of drug-resistant TB regimens, but the recommended dose is not evidence based. Pharmacokinetic data from relevant patient populations are needed to inform dose optimization. OBJECTIVES: To determine clofazimine exposure, evaluate covariate effects on variability, and simulate exposures for different dosing strategies in South African TB patients. PATIENTS AND METHODS: Clinical and pharmacokinetic data were obtained from participants with pulmonary TB enrolled in two studies with intensive and sparse sampling for up to 6 months. 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 mg/L. RESULTS: 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 L/h and peripheral volume 10 500 L 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 mg daily for 2 weeks would achieve average daily concentrations above a target efficacy concentration 37 days earlier in a typical TB participant. CONCLUSIONS: 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.","journal":"Journal of Antimicrobial Chemotherapy","year":2020,"id":58873,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":70,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8115,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308893,"name":"Sean Wasserman","orcid":"0000-0002-3508-6719","position":1,"is_corresponding":false},{"id":308894,"name":"James C.M. Brust","orcid":"0000-0003-3362-1818","position":2,"is_corresponding":false},{"id":308895,"name":"Neel R. Gandhi","orcid":"0000-0002-1665-299X","position":3,"is_corresponding":false},{"id":292884,"name":"Graeme Meintjes","orcid":"0000-0003-1196-4414","position":4,"is_corresponding":false},{"id":310063,"name":"Daniel E. Everitt","orcid":null,"position":5,"is_corresponding":false},{"id":308896,"name":"Andreas H. Diacon","orcid":"0000-0001-8641-6792","position":6,"is_corresponding":false},{"id":308897,"name":"Rodney Dawson","orcid":"0000-0001-9804-1588","position":7,"is_corresponding":false},{"id":308898,"name":"Lubbe Wiesner","orcid":"0000-0002-9070-8699","position":8,"is_corresponding":false},{"id":308899,"name":"Elin M. Svensson","orcid":"0000-0002-0093-6445","position":9,"is_corresponding":false},{"id":110248,"name":"Gary Maartens","orcid":"0000-0003-3080-6606","position":10,"is_corresponding":false},{"id":308900,"name":"Paolo Denti","orcid":"0000-0001-7494-079X","position":11,"is_corresponding":false},{"id":308892,"name":"Mahmoud Tareq Abdelwahab","orcid":"0000-0002-2134-8749","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T21:07:33.416320Z","pmid":"32747933","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}