Pharmacokinetics of anti-TB drugs in Malawian children: reconsidering the role of ethambutol

The Journal of Antimicrobial Chemotherapy
R MlothaS A Ward

Abstract

Current guidelines for dosing of anti-TB drugs in children advocate higher doses for rifampicin and isoniazid despite limited availability of paediatric data on the pharmacokinetics of these drugs, especially from Africa, where the burden of childhood disease remains high. Thirty children aged 6 months to 15 years underwent intensive pharmacokinetic sampling for first-line anti-TB drugs at Queen Elizabeth Central Hospital, Blantyre, Malawi. Rifampicin, isoniazid, pyrazinamide and ethambutol were dosed at 10, 5, 25 and 20 mg/kg, respectively. Plasma drug concentrations were determined using sensitive, validated bioanalytical methods and summary pharmacokinetic parameters were estimated using non-compartmental analysis. The median (IQR) Cmax was 2.90 (2.08-3.43), 3.37 (2.55-4.59), 34.60 (32.30-40.90) and 1.20 (0.85-1.68) mg/L while the median (IQR) AUC0-∞ was 16.92 (11.10-22.74), 11.48 (7.35-18.93), 333.50 (279.50-487.2) and 8.65 (5.96-11.47) mg·h/L for rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. For all drugs, pharmacokinetic parameters relating to drug absorption and exposure were lower than those published for adults, though similar to existing paediatric data from sub-Saharan Africa. Weight and/or dose p...Continue Reading

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Citations

Nov 3, 2016·Expert Review of Clinical Pharmacology·Bella Devaleenal DanielSoumya Swaminathan
Nov 28, 2015·British Journal of Clinical Pharmacology·A SchipaniG Davies
May 4, 2017·Antimicrobial Agents and Chemotherapy·Derek J SloanGeraint R Davies
Aug 8, 2015·Antimicrobial Agents and Chemotherapy·J J van OosterhoutS Ward
Nov 27, 2018·Expert Review of Clinical Pharmacology·Fiona V CresswellReinout Van Crevel
Jun 17, 2016·European Journal of Clinical Pharmacology·Roger K VerbeeckTim W Rennie
Mar 28, 2019·Indian Journal of Pediatrics·Aparna MukherjeeS K Kabra

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