{"doi":"10.1128/aac.01381-21","title":"Linezolid Population Pharmacokinetics in South African Adults with Drug-Resistant Tuberculosis","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. Data were obtained from pharmacokinetic substudies in a randomized controlled trial and an observational cohort study, both of which enrolled adults with drug-resistant pulmonary tuberculosis. Participants underwent intensive and sparse plasma sampling. We analyzed linezolid concentration data using nonlinear mixed-effects modeling and performed simulations to estimate attainment of putative efficacy and toxicity targets. A total of 124 participants provided 444 plasma samples; 116 were on the standard daily dose of 600 mg, while 19 had dose reduction to 300 mg due to adverse events. Sixty-one participants were female, 71 were HIV-positive, and their median weight was 56 kg (interquartile range [IQR], 50 to 63). In the final model, typical values for clearance and central volume were 3.57 liters/h and 40.2 liters, respectively. HIV coinfection had no significant effect on linezolid exposure. Simulations showed that 600-mg dosing achieved the efficacy target (area under the concentration-time curve for the free, unbound fraction of the drug [[Formula: see text] at a MIC level of 0.5 mg/liter) with 96% probability but had 56% probability of exceeding safety target ([Formula: see text]. The 300-mg dose did not achieve adequate efficacy exposures. Our model characterized population pharmacokinetics of linezolid in South African patients with DR-TB and supports the 600-mg daily dose with safety monitoring.","journal":"Antimicrobial Agents and Chemotherapy","year":2021,"id":176716,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9393,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","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":327409,"name":"James C. M. Brust","orcid":null,"position":2,"is_corresponding":false},{"id":528806,"name":"Keertan Dheda","orcid":"0000-0001-7709-5341","position":3,"is_corresponding":false},{"id":308898,"name":"Lubbe Wiesner","orcid":"0000-0002-9070-8699","position":4,"is_corresponding":false},{"id":308895,"name":"Neel R. Gandhi","orcid":"0000-0002-1665-299X","position":5,"is_corresponding":false},{"id":89652,"name":"Robin M. Warren","orcid":"0000-0001-5741-7358","position":6,"is_corresponding":false},{"id":712437,"name":"Frederick A. Sirgel","orcid":null,"position":7,"is_corresponding":false},{"id":292884,"name":"Graeme Meintjes","orcid":"0000-0003-1196-4414","position":8,"is_corresponding":false},{"id":110248,"name":"Gary Maartens","orcid":"0000-0003-3080-6606","position":9,"is_corresponding":false},{"id":308900,"name":"Paolo Denti","orcid":"0000-0001-7494-079X","position":10,"is_corresponding":false},{"id":308892,"name":"Mahmoud Tareq Abdelwahab","orcid":"0000-0002-2134-8749","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:47:23.605867Z","pmid":"34543098","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":[]}