ArticleThe Journal of antimicrobial chemotherapy2022
Population pharmacokinetics of ethambutol in African children: a pooled analysis.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 3 of them syntheses that pooled it.
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Who cites it
6 citing papers in PubMed, 3 syntheses or guidelines pooled it, 8 citations in OpenAlex.
- Pharmacokinetics and Dose Optimization of Ethambutol in Children on First-Line Antituberculosis Therapy: An Individual Patient Data Meta-Analysis.The Journal of infectious diseases · 2026Pooled it
- Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Pooled it
- Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.The European respiratory journal · 2023Pooled it
- Article
- Population pharmacokinetics of pyrazinamide and ethambutol in children with tuberculosis with or without HIV.Antimicrobial agents and chemotherapy · 2026Article
- Population Pharmacokinetics of IV Lidocaine and its Metabolites in Adult Surgical Patients.Pharmaceutical research · 2025Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 5 countries.
Funding
Abstract
objectivesEthambutol 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.
methodsWe 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%).
resultsEthambutol 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.
conclusionsTo 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.
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