Population pharmacokinetics and pharmacodynamics of biapenem in paediatric patients

Objective: To develop a population pharmacokinetic model for biapenem in paediatric patients and to use the parameter estimates to assess pharmacodynamic exposure of common bacterial populations. Methods: Biapenem plasma concentrations (n = 125) from 25 paediatric patients were analysed using nonmem . The parameter estimates were used in a Monte Carlo simulation to predict the exposure time during which the drug concentration remains above the minimum inhibitory concentration. Results: A two‐compartment model fitted the data, and creatinine clearance (CL_cr) and total body weight (TBW) were the most significant covariates. The final model was CL (L/h) = 0·0458 × CL_cr, V_c (L) = 0·162 × TBW, Q (L/h) = 2·05, V_p (L) = 1·73, 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. Biapenem regimens of 5 mg/kg q8h and 10 mg/kg q8h provided sufficient pharmacodynamic exposures to Pseudomonas aeruginosa and Streptococcus pneumoniae in most typical patient populations. Conclusion: These results better define the pharmacokinetics of biapenem and help in the choice of the appropriate dosage regimens for paediatric.