Abdullah A S, Baggot J D
Res Vet Sci. 1986 May;40(3):382-5.
The effect of short term starvation on the disposition kinetics of chloramphenicol was determined in goats. The same dosage level (10 mg kg-1) administered intravenously produced higher serum concentrations in the animals when they were starved than when they were not starved. This could be attributed to the significantly smaller (P less than 0.05) volume of the central compartment. Starvation significantly decreased the rate of elimination of chloramphenicol while the apparent volume of distribution of the drug was not altered. A significant decrease in the body clearance, 1.36 +/- 0.95 ml (min kg)-1 in the starved condition compared with 3.78 +/- 2.19 mg (min kg)-1 in the controls, caused a corresponding increase in the half life of chloramphenicol. The decreased rate of elimination was attributed to decreased hepatic microsomal metabolism since starvation did not change the fraction of the dose excreted unchanged in the urine. The clinical significance of the altered disposition of chloramphenicol is that administration at the usual dosing rate would lead to accumulation of the drug and eventual toxicity.
在山羊身上测定了短期饥饿对氯霉素处置动力学的影响。静脉注射相同剂量水平(10毫克/千克)时,饥饿状态下的动物血清浓度高于未饥饿状态的动物。这可能归因于中央室体积显著减小(P小于0.05)。饥饿显著降低了氯霉素的消除速率,而药物的表观分布容积未改变。机体清除率显著降低,饥饿状态下为1.36±0.95毫升/(分钟·千克),而对照组为3.78±2.19毫克/(分钟·千克),这导致氯霉素的半衰期相应延长。消除速率降低归因于肝微粒体代谢减少,因为饥饿并未改变以原形经尿液排泄的药物剂量比例。氯霉素处置改变的临床意义在于,以常规给药速率给药会导致药物蓄积并最终产生毒性。