{"doi":"10.1093/cid/ciae024","title":"Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis","abstract":"BACKGROUND: Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children. METHODS: Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses. RESULTS: Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax. CONCLUSIONS: Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.","journal":"Clinical Infectious Diseases","year":2024,"id":433623,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":696472,"name":"Belén P. Solans","orcid":"0000-0003-4621-5480","position":1,"is_corresponding":false},{"id":308900,"name":"Paolo Denti","orcid":"0000-0001-7494-079X","position":2,"is_corresponding":false},{"id":667997,"name":"Louvina E. van der Laan","orcid":"0000-0002-3584-7477","position":3,"is_corresponding":false},{"id":231940,"name":"H. Simon Schaaf","orcid":"0000-0001-5755-4133","position":4,"is_corresponding":false},{"id":802124,"name":"Bryan Vonasek","orcid":"0000-0002-5657-0980","position":5,"is_corresponding":false},{"id":105798,"name":"Amyn A. Malik","orcid":"0000-0003-4875-9916","position":6,"is_corresponding":false},{"id":668686,"name":"Heather R. Draper","orcid":null,"position":7,"is_corresponding":false},{"id":387418,"name":"Hamidah Hussain","orcid":"0000-0002-6585-9815","position":8,"is_corresponding":false},{"id":231911,"name":"Anneke C. Hesseling","orcid":"0000-0001-9399-9834","position":9,"is_corresponding":false},{"id":667995,"name":"Anthony J. Garcia‐Prats","orcid":"0000-0002-9280-1950","position":10,"is_corresponding":false},{"id":455381,"name":"Radojka M. Savić","orcid":"0000-0003-3143-5579","position":11,"is_corresponding":false},{"id":926633,"name":"Yasmine White","orcid":"0000-0002-2708-7391","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:59:49.434790Z","pmid":"38340060","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":[]}