SATURABLE RATE OF CEFATRIZINE ABSORPTION AFTER ORAL-ADMINISTRATION TO HUMANS

被引:18
作者
REIGNER, BG [1 ]
COUET, W [1 ]
GUEDES, JP [1 ]
FOURTILLAN, JB [1 ]
TOZER, TN [1 ]
机构
[1] CEMAF,F-86000 POITIERS,FRANCE
来源
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS | 1990年 / 18卷 / 01期
关键词
cefatrizine; Michaelis-Menten equation; saturable absorption rate;
D O I
10.1007/BF01063620
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study examined the absorption kinetics of cefatrizine, an amino-β-lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats. © 1990 Plenum Publishing Corporation.
引用
收藏
页码:17 / 34
页数:18
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