Abstract
Background. Isoniazid (INH) is one of the drugs in the classical therapy
for pulmonary tuberculosis. Several INH population pharmacokinetic
models were established in the last ten years. This systemic review was
performed i) to summarize published population pharmacokinetic (PPK)
models of INH and ii) to summarize and explore identified covariates
influencing the INH pharmacokinetic models. Methods. A search of
publication for population pharmacokinetic analyses of INH either in
healthy volunteers or patients from 2011 to 2021 was conducted in PubMed
databases. Reviews, methodology articles, non-compartmental analysis,
in-vitro, and animal studies, were excluded. Results. 12 studies were
included in this review. INH pharmacokinetics was described as
two-compartment with first-order absorption and elimination in most of
the included studies. In most of the studies, N-acetyltransferase 2
(NAT2 ) genotype polymorphism (n=11) was the most common identified
covariates affecting INH pharmacokinetic parameters. Body weight (n=2)
and body mass index (BMI) (n=1) were the most common significant
covariates retained in the final model. Conclusions . The population
pharmacokinetic of INH has been extensively reviewed and the published
PPK models of INH and its parameters were summarized in this review. The
PPK variability of INH was reported to be explained mainly by the NAT2
genotype polymorphism on the clearance (CL) parameter. This review shows
that to optimise and rationalise the dosing regimen of INH, a patient’s
NAT2 genotype should be considered. Body weight and BMI value should be
taken into consideration when making dosing adjustments for INH to
achieve therapeutic range.