The pharmacokinetics of ceftriaxone based on population pharmacokinetics and the prediction of efficacy in Japanese adults.
OBJECTIVE
By using a population pharmacokinetic analysis method, we predicted the efficacy of Ceftriaxone (CTRX) based on the pharmacokinetics of CTRX in Japanese adults and the sensitivity of infective organisms to CTRX in 2004. In addition, we clarified the difference in efficacy between once-a-day administration and twice-a-day administration.


METHODS
The population pharmacokinetic analysis was based on the serum concentrations of CTRX already published by NONMEM. The possible effect of body weight and age on the pharmacokinetics of CTRX was examined using a model which incorporated the change of a specific protein-binding ratio of CTRX. A Monte Carlo simulation was conducted based on the population pharmacokinetic parameters obtained by this analysis, and thereby the time above MIC (TAM) was determined from the MIC values of CTRX administered once at 0.5, 1, and 2 g and twice at 1 g. The efficacy ratio was predicted from the TAM thus obtained.


RESULTS
Because the time course of serum concentration of CTRX in adult subjects was fitted to a 2-compartment model and both body weight and age were not incorporated as the covariate, the dosing method by which a fixed amount of CTRX is administered to patients has been thought to be adequate. Based on the efficacy ratio estimated from the MIC of CTRX, we have predicted that the once-a-day administration of CTRX even at 0.5g is effective on various infecting organisms.
Iida
Satofumi
S
Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan.
Kinoshita
Haruki
H
Kawanishi
Takehiko
T
Hayashi
Masahiro
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D001419:Bacteria / Q000187:drug effects*; D001835:Body Weight; D002443:Ceftriaxone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D017711:Nonlinear Dynamics; D011485:Protein Binding; D055815:Young Adult
D000900:Anti-Bacterial Agents; D002443:Ceftriaxone