Pharmacokinetic-pharmacodynamic target attainment analysis of biapenem in adult patients: a dosing strategy.

Background: A pharmacokinetic-pharmacodynamic (PK-PD) target attainment analysis to build a dosing strategy for biapenem in adult patients has not been conducted. Methods: A total of 321 plasma concentration samples from 68 adult patients (1–6 samples per patient) were assayed biologically and chromatographically, and used for a population PK modeling and Monte Carlo simulation to assess the probability of attaining the PK-PD target (40% of the time above the minimum inhibitory concentration). Results: The population PK model was based on the standard two-compartment model, and creatinine clearance (Clcr) was the most significant covariate that affected the drug clearance. The Monte Carlo simulation demonstrated that the dosages up to 600 mg Q12H (0.5-h infusions) achieved a PK-PD target attainment probability of ≧90%, which varied with Clcr of the patient and susceptibility of the tested bacterium; however, higher dosage with prolonged infusion time (600 mg Q8H, 3 h infusion) was required for a high probability against Pseudomonas aeruginosa and Haemophilus influenzae isolates in the case of Clcr = 90 ml/min. Conclusion: These results provide guidance for constructing a PK-PD-based strategy for tailoring biapenem regimens in adult patients.