{"doi":"10.1093/cid/ciab725","title":"Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization–Recommended Weight Band Doses and Formulations","abstract":"BACKGROUND: Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. METHODS: Children weighing 4.0-7.9, 8.0-11.9, 12.0-15.9, or 16.0-24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0-36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. RESULTS: In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4-6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1-45.1), 16.7 (9.2-25.9), 317 (263-399), and 9.5 (7.5-11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0-7.9-, 8-11.9-, and ≥25-kg weight bands, isoniazid in the 4.0-7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. CONCLUSIONS: Recommended weight band-based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization-recommended doses requires further evaluation.","journal":"Clinical Infectious Diseases","year":2021,"id":167470,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7867,"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":694924,"name":"Anna Turkova","orcid":"0000-0002-7008-4145","position":1,"is_corresponding":false},{"id":231911,"name":"Anneke C. Hesseling","orcid":"0000-0001-9399-9834","position":2,"is_corresponding":false},{"id":695788,"name":"Kevin Zimba","orcid":null,"position":3,"is_corresponding":false},{"id":695789,"name":"Marieke van der Zalm","orcid":null,"position":4,"is_corresponding":false},{"id":695790,"name":"Monica Kapasa","orcid":null,"position":5,"is_corresponding":false},{"id":694925,"name":"Megan Palmer","orcid":"0000-0002-2534-2483","position":6,"is_corresponding":false},{"id":371675,"name":"Maxwell Chirehwa","orcid":"0000-0002-1685-4882","position":7,"is_corresponding":false},{"id":308898,"name":"Lubbe Wiesner","orcid":"0000-0002-9070-8699","position":8,"is_corresponding":false},{"id":475682,"name":"Eric Wobudeya","orcid":"0000-0001-9574-5539","position":9,"is_corresponding":false},{"id":326391,"name":"Aarti Kinikar","orcid":"0000-0001-9466-1130","position":10,"is_corresponding":false},{"id":326404,"name":"Vidya Mave","orcid":"0000-0001-8509-4517","position":11,"is_corresponding":false},{"id":340197,"name":"Syed Hissar","orcid":"0000-0003-0905-1552","position":12,"is_corresponding":false},{"id":475683,"name":"Louise Choo","orcid":"0000-0003-4040-1522","position":13,"is_corresponding":false},{"id":476377,"name":"Kristen LeBeau","orcid":null,"position":14,"is_corresponding":false},{"id":694926,"name":"Veronica Mulenga","orcid":"0000-0003-1843-8169","position":15,"is_corresponding":false},{"id":695791,"name":"R. A. Aarnoutse","orcid":null,"position":16,"is_corresponding":false},{"id":475685,"name":"Diana M. Gibb","orcid":"0000-0002-9738-5490","position":17,"is_corresponding":false},{"id":371679,"name":"Helen McIlleron","orcid":"0000-0002-0982-6226","position":18,"is_corresponding":false},{"id":694923,"name":"Chishala Chabala","orcid":"0000-0002-5551-5752","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:45:58.359801Z","pmid":"34420049","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":[]}