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Population Pharmacokinetics of Isoniazid: A Systemic Review
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  • Wen Rui Tan,
  • Siti Maisharah Sheikh Ghadzi,
  • Sabariah Noor Harun,
  • Irfhan Ali Hyder Al
Wen Rui Tan
Universiti Sains Malaysia
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Siti Maisharah Sheikh Ghadzi
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Sabariah Noor Harun

Corresponding Author:[email protected]

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Irfhan Ali Hyder Al
Penang General Hospital,
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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.