Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization–Recommended Weight Band Doses and Formulations
Autor: | Robb Aarnoutse, Chishala Chabala, Helen McIlleron, Kevin M Zimba, Vidya Mave, Marieke M. van der Zalm, Anneke C. Hesseling, Anna Turkova, Lubbe Wiesner, Veronica Mulenga, Aarti Kinikar, Megan Palmer, Louise Choo, Kristen Lebeau, Eric Wobudeya, Syed Hissar, Diana M. Gibb, Maxwell Chirehwa, Monica Kapasa |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male Microbiology (medical) medicine.medical_specialty Tuberculosis Fixed-dose combination Antitubercular Agents World Health Organization Pharmacokinetics Internal medicine Isoniazid medicine Humans Dosing Child Ethambutol business.industry Pyrazinamide medicine.disease lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Infectious Diseases Child Preschool Female Rifampin business Rifampicin medicine.drug |
Zdroj: | Clinical Infectious Diseases, 74, 1767-1775 Clinical Infectious Diseases, 74, 10, pp. 1767-1775 |
ISSN: | 1537-6591 1058-4838 |
DOI: | 10.1093/cid/ciab725 |
Popis: | 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 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. |
Databáze: | OpenAIRE |
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