甲苯磺丁脲作为大鼠体内酶诱导和酶抑制研究的模型药物。
Tolbutamide as a model drug for the study of enzyme induction and enzyme inhibition in the rat.
作者信息
Back D J, Sutcliffe F, Tjia J F
出版信息
Br J Pharmacol. 1984 Mar;81(3):557-62. doi: 10.1111/j.1476-5381.1984.tb10109.x.
Abstract
The effects of various drugs on the pharmacokinetics of tolbutamide have been examined in the rat. Phenobarbitone pretreatment caused a significant decrease in half life and area under the curve (AUC) and a significant increase in clearance and volume of distribution (Vd). Acute administration of primaquine significantly increased half life and AUC and decreased clearance. In contrast, the related animoquinolone chloroquine, was without effect. Acute administration of cimetidine produced similar changes to primaquine but of lesser magnitude. Formation of the major metabolite hydroxytolbutamide, was markedly enhanced by phenobarbitone and reduced by primaquine and cimetidine. We conclude that due to its single pathway of metabolism, tolbutamide is a good substrate to use when examining pharmacokinetic interactions involving hepatic enzyme induction and inhibition.
摘要
已在大鼠中研究了各种药物对甲苯磺丁脲药代动力学的影响。苯巴比妥预处理导致半衰期和曲线下面积（AUC）显著降低，清除率和分布容积（Vd）显著增加。急性给予伯氨喹显著增加了半衰期和AUC，并降低了清除率。相比之下，相关的氨基喹啉氯喹则无作用。急性给予西咪替丁产生了与伯氨喹相似但程度较小的变化。主要代谢产物羟基甲苯磺丁脲的形成，被苯巴比妥显著增强，而被伯氨喹和西咪替丁降低。我们得出结论，由于甲苯磺丁脲单一的代谢途径，在研究涉及肝酶诱导和抑制的药代动力学相互作用时，它是一种很好的研究底物。
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