systematic-review-of-population-pharmacokinetic-models-of-isoniazid-in-children-and-adults-with-tuberculosis

Abstract

Introduction: Isoniazid (INH) is one of the first-line anti-tuberculosis (anti-TB) drugs that have both bactericidal and bacteriostatic properties depending on the rate of mycobacterial growth. Several population pharmacokinetic (PPK) models of INH were established. This systemic review aims to summarise published PPK parameters of INH in the models and to identify covariates influencing the INH pharmacokinetic parameters of models. Method: A search of publications for PPK analyses of INH in volunteers or TB patients from 2011 to 2021 was conducted in PubMed and Scopus databases. Reviews, methodology articles, non-compartmental analysis, in vitro, and animal studies were excluded. Result: Twelve studies were included in this review. Most of the included studies described the pharmacokinetics of INH as two-compartmental with first-order absorption and elimination in most of the included studies. Eleven studies reported N-acetyltransferase 2 (NAT2) genotype polymorphism as the most common significant covariate affecting the pharmacokinetic parameters of INH. Other common significant covariates reported include body weight (n = 2) and body mass index (BMI) (n = 1). Conclusion: The variability of population clearance parameters of INH was explained mainly by the NAT2 genotype polymorphism. This indicates that to optimise and rationalise the dosing regimen of INH, a patient's NAT2 genotype should be considered. At the same time, body weight and BMI values should be considered when making dosing adjustments for INH to achieve the therapeutic range.