THEORETICAL-MODEL FOR BOTH SATURABLE RATE AND EXTENT OF ABSORPTION - SIMULATIONS OF CEFATRIZINE DATA

被引:14
作者
COUET, WR
REIGNER, BG
GUEDES, JP
TOZER, TN
机构
[1] UNIV CALIF SAN FRANCISCO,SCH PHARM,SAN FRANCISCO,CA 94143
[2] CEMAF,F-86000 POITIERS,FRANCE
[3] LYCEE DESCARTES,F-37000 TOURS,FRANCE
来源
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS | 1991年 / 19卷 / 03期
关键词
MICHAELIS-MENTEN EQUATION; SATURABLE ABSORPTION; CEFATRIZINE; SIMULATIONS OF ABSORPTION MODELS; AMINO-BETA-LACTAM ABSORPTION;
D O I
10.1007/BF03036251
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A pharmacokinetic model incorporating saturable rate of absorption of the Michaelis-Menten type was recently developed to fit cefatrizine (CFZ) plasma concentrations with time following oral administration of 500-mg capsules to humans. This model (MM) was statistically superior to models incorporating either first-order or zero-order absorption. However, the MM model does not predict the reduction in extent of absorption with dose observed in vivo. In this study, a model is proposed in which a time constraint, DELTA-t, is added to the MM model. This new model (MM-DELTA-t) is tested with data following doses of 250, 500, and 1000 mg of CFZ. When DELTA-t is set to 1.5 hr, the predicted relative changes with dose in bioavailability, F. peak plasma concentration, C(max), the time at which the peak concentration occurs, t(max), and the mean absorption time, MAT, are generally in good agreement with the experimental data. The time interval of 1.5 hr is compatible with passage by a limited region within the small intestine where drug is absorbed by a facilitated transport mechanism. Influence of each absorption model parameter (V(max), K(m), and DELTA-t) on total area under the concentration versus time curve (AUC), F, C(max), and t(max), is assessed by simulation. The MM-DELTA-t model is able to summarize the nonlinearity observed in both rate and extent of absorption.
引用
收藏
页码:271 / 285
页数:15
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