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Population pharmacokinetics and pharmacodynamics of biapenem in paediatric patients
Author(s) -
Ikawa K.,
Morikawa N.,
Ikeda K.,
Miki M.,
Nishimura S.,
Kobayashi M.
Publication year - 2008
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2008.00908.x
Subject(s) - pharmacodynamics , pharmacokinetics , medicine , population pharmacokinetics , population , pharmacology , environmental health
Summary 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.