Dataset Information

Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial.

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 and methods

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 ∼35 mg/kg (days 1-14) and ∼50 mg/kg (day 15) for cohort 2 and ∼60 mg/kg (days 1-14) and ∼75 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.

SUBMITTER: Garcia-Prats AJ

PROVIDER: S-EPMC8598292 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial.

Garcia-Prats Anthony J AJ Svensson Elin M EM Winckler Jana J Draper Heather R HR Fairlie Lee L van der Laan Louvina E LE Masenya Masebole M Schaaf H Simon HS Wiesner Lubbe L Norman Jennifer J Aarnoutse Rob E RE Karlsson Mats O MO Denti Paolo P Hesseling Anneke C AC

The Journal of antimicrobial chemotherapy 20211101 12

<h4>Background</h4>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.<h4>Objectives</h4>To characterize the pharmacokinetics and safety of high rifampicin doses in children with drug-susceptible TB.<h4>Patients and methods</h4>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 targe ...[more]

PMID: 34529779

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Dataset Information

Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial.

Background

Objectives

Patients and methods

Results

Conclusions

Publications

Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial.

Similar Datasets

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