Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial.
J Antimicrob Chemother
; 76(12): 3237-3246, 2021 11 12.
Article
em En
| MEDLINE
| ID: mdl-34529779
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 ANDMETHODS:
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 â¼35 mg/kg (days 1-14) and â¼50 mg/kg (day 15) for cohort 2 and â¼60 mg/kg (days 1-14) and â¼75 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Rifampina
Limite:
Child
/
Child, preschool
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Humans
/
Infant
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
África do Sul