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Population Pharmacokinetics of Isoniazid in Chinese Tuberculosis Patients

??OBJECTIVE To characterize the population pharmacokinetics of isoniazid in Chinese tuberculosis patients. METHODS A total of 321 serum samples were obtained from 201 patients receiving oral doses of isoniazid. The effects of 16 covariates including demographics and blood tests to isoniazid??s pharmacokinetics were evaluated. Data analysis was performed using non-linear mixed effects modeling (NONMEM). Prediction-corrected visual prediction check was performed for model evaluation. RESULTS A two-compartment model with first-order absorption and linear elimination can well fit the isoniazid concentration-time data. A ??MIXTURE?? model was used to separate the subpopulation of ??subgroup A?? and ??subgroup B??. Typical clearance of the two subpopulations were 82.7 and 19.3 L??h^-1, respectively. CONCLUSION Model validation shows the final model is reliable, which could be used for individualized treatment.