Pharmacokinetic - pharmacodynamic properties of Rifampicin in pulmonary tuberculosis patients

Abstract

Objectives: Rifampicin is a key drug to kill M. tuberculosis and prevent recurrence in tuberculosis management. This research aims to determine pharmacokinetic (PK) and pharmacodynamic (PD) properties of Rifampicin in nonmultidrug-resistant tuberculosis (non-MDRTB) patients and the proportion of patients who achieve the proposed target of AUC/MIC. Methods: venus blood samples were collected at certain time points of 135 new cases or retreatment non-MDRTB patients to measure the concentration of Rifampicin in plasma by HPLC-MS/MS. In addition, patients’ sputum samples were collected to isolate M. tuberculosis strains for the determination of MIC to Rifampicin. Population pharmacokinetic model and estimated individual parameter values were built by Monolix2018R1 and the R package Simulx. The MIC was determinated by proportional 48-well microplate in Middlebrook 7H11. Finally, individual AUC/ MIC were compared with the target of AUC/MIC>271. Results and conclusions: one-compartment population PK model characterised by transit compartment absorption was built. The mean and median AUC values of population were 50.565 and 45.99 mg.h/l, respectively. The MIC values of 123 patients were almost in range of 0.25-1 µg/ml. Only 16/123 patients achieved the proposed target of AUC/MIC>271; the ratio lowered significantly in patients with MIC over 0.25 µg/ml and dropped to 0% in those with MIC of 1 µg/ml and higher. PK and PD properties of Rifampicin showed large variability between patients; however, the exposure can be deemed as suboptimal, thus leading the need to adjust dose and r