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 x CL(cr), V(c) (L) = 0.162 x 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.