Population Pharmacokinetics of Rifampicin in Chinese Patients With Pulmonary Tuberculosis


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Abstract

Rifampicin (RIF) induces cytochrome P450, which in turn catalyzes drug metabolism; however, pharmacokinetic studies on this phenomenon in the Chinese population, especially in the context of disease, are limited. Therefore, we sought to establish population-based pharmacokinetic models of RIF in a Chinese population with pulmonary tuberculosis (TB). Clinical data were retrospectively collected from 54 patients with pulmonary TB and analyzed alongside RIF blood levels from 95 samples collected prior to RIF administration and between 2 and 12 hours after treatment. HPLC was used to measure serum RIF concentrations. A nonlinear mixed model used to characterize RIF pharmacokinetics and the data generated from the present study were validated using a bootstrap method. Covariates, including demographics, as well as hematological and biological indicators were analyzed. We observed a 1-compartment model with first-order absorption. Typical population values of apparent clearance (CL/F) and apparent volume of distribution (VD/F) were 4.02 L/h and 57.8 L, respectively. No covariate significantly changed the parameters of CL/F and VD. The present study may serve as a foundation for individualized therapy and offer a basis for pharmacokinetic-pharmacodynamic (PK-PD) analysis.

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