Simulation of pyrazinamide pharmacokinetics/pharmacodynamics in Vietnamese pulmonary tuberculosis patients

Abstract

Background: Pyrazinamide (PZA) plays an important role in the first-line regimens against tuberculosis and needs optimisation. This research aims to determine the ability to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets of PZA in the treatment of pulmonary tuberculosis. Method: A total of 516 blood samples from 129 drug-susceptible pulmonary tuberculosis patients were collected to record PZA concentration-time data, then, a population pharmacokinetic model for pyrazinamide was built using the software MONOLIX 2019R2; Monte Carlo simulation was performed to attain PK/PD target attainment ratios of various total body weight and fat-free mass (FFM) based regimens. Result: PK/PD target attainment ratios increased along with higher dosage levels. At MIC levels of ≥50 μg/ml, a dose of 40 mg/kg was required for over 80% of patient to achieve the target area under the curve/minimum inhibitory concentration (AUC/MIC); dosage at 30 mg/kg or 35 mg/kg FFM should ensure over 90% of patients achieve AUC_0-24 and C_max targets. An FFM-based dosing strategy shows results compared to total body weight-based dosing. Conclusion: FFM-based dosing strategy improved PK/PD target attainment ratios.