title: Indications for a ceftriaxone dosing regimen in Japanese paediatric patients using population pharmacokinetic/pharmacodynamic analysis and simulation.
abstract: OBJECTIVE
  The objective of this study was to build a ceftriaxone population pharmacokinetic model for Japanese paediatric patients and to examine the dosing regimen of ceftriaxone based on pharmacokinetic/pharmacodynamic (PK/PD) analysis.
  
  
  METHODS
  The population pharmacokinetic analysis using NONMEM was based on published serum concentrations of ceftriaxone. A Monte Carlo simulation was examined to evaluate the time above the minimum inhibitory concentration (TAM) in 20 and 60 mg/kg body weight dose regimen using the population pharmacokinetic parameters.
  
  
  RESULTS
  The time course of the serum concentration of ceftriaxone in paediatric patients was fitted to a two-compartment model and body weight was incorporated to pharmacokinetic parameters as the covariate. Based on the percent TAM estimated from the final population pharmacokinetic model and the minimum inhibitory concentration (MIC) of ceftriaxone in 2004, we have predicted that the once daily administration of 20 mg/kg ceftriaxone would be effective on various infecting organisms.
  
  
  CONCLUSIONS
  A population pharmacokinetic model of ceftriaxone was built for Japanese paediatric patients based on the available data. The estimated PK/PD result confirmed the appropriateness of once daily dose of 20 mg/kg. In some patients for whom no efficacy was observed at 20 mg/kg, an increase to 60 mg/kg may be required.
authors.affiliation: Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. iidastf@chugai-pharm.co.jp
authors.forename: Satofumi
authors.initials: S
authors.lastname: Iida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kawanishi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D001835:Body Weight; D002443:Ceftriaxone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D017711:Nonlinear Dynamics; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone