Full Length Research Paper
Abstract
Until recently, the dose of isoniazid used to treat tuberculosis was the same for all patient groups. However, the pharmacokinetic profile of isoniazid varies across different populations. A comparative, observational, single-dose, 5 h study was conducted evaluating the pharmacokinetics of isoniazid in Ethiopian children. Pharmacokinetic parameters for a dose of 5 mg/kg and NAT2 genotype were determined in 29 children with tuberculosis (<15 years, with mean age of 8.6). Initially, univariate analyses evaluated covariates that exhibited associations (p < 0.2) with isoniazid pharmacokinetic parameters. Covariates with associations, acetylator genotype (p < 0.01) and age (p < 0.1) were further analysed with multiple linear regression. Sixteen (55%) were genotyped as rapid and 13 (45%) as slow acetylators. Four rapid acetylators had 2 and 3 h post-dose concentrations of < 3 and 1.5 ug/ml, respectively. Multiple linear regression analyses revealed acetylator status to be the only predictor of k, area under the curve (AUC2→5h), and isoniazid concentrations at 2, 3, 4 and 5 h. The mean values of these variables were also found to differ between genotypes (p < 0.0025). These findings reaffirm that 5 mg/kg isoniazid dose may not provide adequate plasma drug levels in all paediatric patients. Thus, isoniazid dose for children should be higher than 5 mg/kg body weight to cover the diverse acetylation kinetics.
Key words: Acetylator status, paediatric tuberculosis, isoniazid, pharmacokinetics, NAT2, Ethiopia.
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