Pharmacokinetic-pharmacodynamic target attainment analysis of cefozopran in Japanese adult patients

摘要

This study aimed to perform a pharmacokinetic-pharmacodynamic (PK-PD) target attainment analysis to create a dosing strategy for cefozopran in Japanese adult patients. A total of 145 plasma concentration samples from 32 adult patients were used for a population pharmacokinetic modeling and Monte Carlo simulation to assess the probability of attaining the PK-PD target (70% of the time above the minimum inhibitory concentration for the bacterium). The final population pharmacokinetic model was based on a two-compartment model, and creatinine clearance (Clcr) and body weight (BW) were the most significant covariates: Cl(l/h) = 0.0263 × Clcr + 1.49, V c(l) = 0.185 × BW0.931, Q(l/h) = 4.55, V p(l) = 5.86, where Cl is the clearance, V c is the volume of distribution of the central compartment, Q is the intercompartmental clearance, and V p is the volume of distribution of the peripheral compartment. The Monte Carlo simulation demonstrated that 1 g q 12 h achieved a PK-PD target attainment probability of ≥85% against Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae isolates. However, against Haemophilus influenzae and Pseudomonas aeruginosa isolates, 1 g q 8 h and (2 g, 1 g, 1 g) q 8 h were required to achieve a high probability, which value varied with the Clcr and BW of the patient. These results provide a PK-PD-based strategy for tailoring cefozopran regimens in Japanese adult patients.