{"doi":"10.1093/jac/dkab336","title":"Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial","abstract":"BACKGROUND: Rifampicin doses of 40 mg/kg in adults are safe and well tolerated, may shorten anti-TB treatment and improve outcomes, but have not been evaluated in children. OBJECTIVES: To characterize the pharmacokinetics and safety of high rifampicin doses in children with drug-susceptible TB. PATIENTS AND METHODS: The Opti-Rif trial enrolled dosing cohorts of 20 children aged 0-12 years, with incremental dose escalation with each subsequent cohort, until achievement of target exposures or safety concerns. Cohort 1 opened with a rifampicin dose of 15 mg/kg for 14 days, with a single higher dose (35 mg/kg) on day 15. Pharmacokinetic data from days 14 and 15 were analysed using population modelling and safety data reviewed. Incrementally increased rifampicin doses for the next cohort (days 1-14 and day 15) were simulated from the updated model, up to the dose expected to achieve the target exposure [235 mg/L·h, the geometric mean area under the concentration-time curve from 0 to 24 h (AUC0-24) among adults receiving a 35 mg/kg dose]. RESULTS: Sixty-two children were enrolled in three cohorts. The median age overall was 2.1 years (range = 0.4-11.7). Evaluated doses were ∼35 mg/kg (days 1-14) and ∼50 mg/kg (day 15) for cohort 2 and ∼60 mg/kg (days 1-14) and ∼75 mg/kg (day 15) for cohort 3. Approximately half of participants had an adverse event related to study rifampicin; none was grade 3 or higher. A 65-70 mg/kg rifampicin dose was needed in children to reach the target exposure. CONCLUSIONS: High rifampicin doses in children achieved target exposures and the doses evaluated were safe over 2 weeks.","journal":"Journal of Antimicrobial Chemotherapy","year":2021,"id":158657,"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":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9158,"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":308899,"name":"Elin M. Svensson","orcid":"0000-0002-0093-6445","position":1,"is_corresponding":false},{"id":667996,"name":"Jana Winckler","orcid":"0000-0003-1218-468X","position":2,"is_corresponding":false},{"id":668686,"name":"Heather R. Draper","orcid":null,"position":3,"is_corresponding":false},{"id":473780,"name":"Lee Fairlie","orcid":"0000-0001-5327-1734","position":4,"is_corresponding":false},{"id":667997,"name":"Louvina E. van der Laan","orcid":"0000-0002-3584-7477","position":5,"is_corresponding":false},{"id":616509,"name":"Masebole Masenya","orcid":null,"position":6,"is_corresponding":false},{"id":231940,"name":"H. Simon Schaaf","orcid":"0000-0001-5755-4133","position":7,"is_corresponding":false},{"id":308898,"name":"Lubbe Wiesner","orcid":"0000-0002-9070-8699","position":8,"is_corresponding":false},{"id":472117,"name":"Jennifer Norman","orcid":"0000-0002-6903-6031","position":9,"is_corresponding":false},{"id":644488,"name":"Rob E. Aarnoutse","orcid":"0000-0001-8925-969X","position":10,"is_corresponding":false},{"id":632169,"name":"Mats O. Karlsson","orcid":"0000-0003-1258-8297","position":11,"is_corresponding":false},{"id":308900,"name":"Paolo Denti","orcid":"0000-0001-7494-079X","position":12,"is_corresponding":false},{"id":231911,"name":"Anneke C. Hesseling","orcid":"0000-0001-9399-9834","position":13,"is_corresponding":false},{"id":667995,"name":"Anthony J. Garcia‐Prats","orcid":"0000-0002-9280-1950","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-18T23:44:30.791367Z","pmid":"34529779","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":[]}