{"doi":"10.1093/jac/dkac127","title":"Population pharmacokinetics of ethambutol in African children: a pooled analysis","abstract":"OBJECTIVES: Ethambutol protects against the development of resistance to co-administered drugs in the intensive phase of first-line anti-TB treatment in children. It is especially relevant in settings with a high prevalence of HIV or isoniazid resistance. We describe the population pharmacokinetics of ethambutol in children with TB to guide dosing in this population. METHODS: We pooled data from 188 intensively sampled children from the DATiC, DNDi and SHINE studies, who received 15-25 mg/kg ethambutol daily according to WHO guidelines. The median (range) age and weight of the cohort were 1.9 (0.3-12.6) years and 9.6 (3.9-34.5) kg, respectively. Children with HIV (HIV+; n = 103) received ART (lopinavir/ritonavir in 92%). RESULTS: Ethambutol pharmacokinetics were best described by a two-compartment model with first-order elimination and absorption transit compartments. Clearance was estimated to reach 50% of its mature value by 2 months after birth and 99% by 3 years. Typical steady-state apparent clearance in a 10 kg child was 15.9 L/h. In HIV+ children on lopinavir/ritonavir, bioavailability was reduced by 32% [median (IQR) steady-state Cmax = 0.882 (0.669-1.28) versus 1.66 (1.21-2.15) mg/L). In young children, bioavailability correlated with age. At birth, bioavailability was 73.1% of that in children 3.16 years or older. CONCLUSIONS: To obtain exposure within the 2-6 mg/L recommended range for Cmax, the current doses must be doubled (or tripled with HIV+ children on lopinavir/ritonavir) for paediatric patients. This raises concerns regarding the potential for ocular toxicity, which would require evaluation.","journal":"Journal of Antimicrobial Chemotherapy","year":2022,"id":266468,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.625,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":371679,"name":"Helen McIlleron","orcid":"0000-0002-0982-6226","position":1,"is_corresponding":false},{"id":308892,"name":"Mahmoud Tareq Abdelwahab","orcid":"0000-0002-2134-8749","position":2,"is_corresponding":false},{"id":354231,"name":"Adrie Bekker","orcid":"0000-0003-3836-3432","position":3,"is_corresponding":false},{"id":231911,"name":"Anneke C. Hesseling","orcid":"0000-0001-9399-9834","position":4,"is_corresponding":false},{"id":694923,"name":"Chishala Chabala","orcid":"0000-0002-5551-5752","position":5,"is_corresponding":false},{"id":875261,"name":"Geraint Davies","orcid":"0000-0002-3819-490X","position":6,"is_corresponding":false},{"id":5182,"name":"Heather J. Zar","orcid":"0000-0002-9046-759X","position":7,"is_corresponding":false},{"id":328863,"name":"Helena Rabie","orcid":"0000-0001-6336-2963","position":8,"is_corresponding":false},{"id":671414,"name":"Isabelle Andrieux‐Meyer","orcid":null,"position":9,"is_corresponding":false},{"id":551799,"name":"Janice Lee","orcid":"0000-0002-0289-2212","position":10,"is_corresponding":false},{"id":308898,"name":"Lubbe Wiesner","orcid":"0000-0002-9070-8699","position":11,"is_corresponding":false},{"id":295667,"name":"Mark F. Cotton","orcid":"0000-0003-2559-6034","position":12,"is_corresponding":false},{"id":308900,"name":"Paolo Denti","orcid":"0000-0001-7494-079X","position":13,"is_corresponding":false},{"id":875274,"name":"Tjokosela Tikiso","orcid":"0000-0003-2488-7390","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T00:26:58.102271Z","pmid":"35466379","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":[]}