Archives of Pharmacal Research
- Volume 13 Issue 3
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- Pages.227-232
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- 1990
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- 0253-6269(pISSN)
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- 1976-3786(eISSN)
Physiological Pharmacokinetic Model of Ceftriaxone Disposition in the Rat and the Effect of Caffeine on the Model
- Kwon, Kwang-Il (College of Pharmacy, Chung Nam National University) ;
- Bourne, David-W.A. (College of Pharmacy, University of Oklahoma)
- Published : 1990.09.01
Abstract
A Physiologically based pharmacokinetic model was used to describe the distribition and elimination of cefriazone in the rat. To validate the practical application of the model, the effect of cffeine on the model was also examined. The model consisted of eleven compartments representing the major sites for ceftriaxone distribution including carcass which served as a residual compartment. Elimination was represented by renal and hepatic (metabolic biliary )excretion with GI secretion and re-absorption. The drug concentrations in most of the tissues were simulated using flow limited equations while brain levels were simulated using membrane limited passive diffusion distribution. The experimental data were obtained by averaging the concentration of drug in the plasma and tissues of five rats after i. v. injection of cefriazone 100 mg/kg without and with caffeine 20 mg/kg. The data for the amount of ceftriazone excreted in urine and gut contents were used to apportion total body clearance. HPLC with UV detection was used for the assay with 0.1-0.2