Population pharmacokinetics and dosing of ethionamide in children with tuberculosis.

Population pharmacokinetics and dosing of ethionamide in children with tuberculosis. Antimicrob Agents Chemother. 2019 Dec 23;: Authors: Bjugård Nyberg H, Draper HR, Garcia-Prats AJ, Thee S, Bekker A, Zar HJ, Hooker AC, Schaaf HS, McIlleron H, Hesseling AC, Denti P Abstract Ethionamide has proven efficacy against both drug-susceptible and some drug-resistant strains of Mycobacterium tuberculosis Limited information is available on its pharmacokinetics in children, and current doses are extrapolated from weight-based adult doses. Paediatric doses based on more robust evidence is expected to improve antituberculosis treatment, especially in small children. In this analysis, ethionamide concentrations in children were pooled from 2 observational clinical studies conducted in Cape Town, South Africa. All children received ethionamide once-daily with weight-based dosing of approximately 20 mg/kg [range 10.4-25.3], in combination with other first- or second-line antituberculosis medications, and with antiretroviral therapy in cases of HIV co-infection. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modelling. MDR-PK1 contributed 110 children on treatment for multidrug-resistant tuberculosis, while DATiC contributed 9 children treated for drug-susceptible tuberculosis, with a combined median [range] age of 2.6 years [0.23-15], weight of 12.5 kg [2.5-66]. A one-compartment, transit absorption model with first-order ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research