First-pass metabolism of inspired ethyl acetate in the upper respiratory tracts of the F344 rat and Syrian hamster.
First-pass metabolism of inspired ethyl acetate in the upper respiratory tracts of the F344 rat and Syrian hamster.
复制标题
F344 大鼠和叙利亚仓鼠上呼吸道中吸入的乙酸乙酯的首过代谢。
DOI：
10.1016/0041-008x(90)90031-o
复制
发表时间：
1990
影响因子：
3.8
通讯作者：
Morris,JB
中科院分区：
文献类型：
--
作者：
Morris,JB
鼻组织含有大量的羧酸酯酶，但其在吸入的酯蒸气代谢中的确切作用尚不清楚。本研究旨在定量F344大鼠和叙利亚仓鼠上呼吸道（URT）中吸入乙酸乙酯的代谢程度。在恒定速度单向流动条件下，在这些物种的手术分离的URT中测量乙酸乙酯沉积。代谢的程度估计数学建模的基础上一个简单的静脉平衡的方法，并通过直接比较的沉积效率在幼稚和羧酸酯酶抑制的动物。大鼠URT中乙酸乙酯沉积效率平均为10 - 35%，仓鼠中为36 - 72%。羧酸酯酶抑制减少沉积在这两个物种。未处理动物和抑制动物之间的建模工作和直接比较均表明，在两个种属的URT中代谢了大量沉积的乙酸乙酯，仓鼠中的代谢程度更明显。具体而言，40-65%的沉积乙酸乙酯在大鼠URT中代谢，而仓鼠中为63-90%。这种首过代谢（i）增加了URT沉积效率;（ii）导致URT组织中产生高代谢物水平;和（iii）减少了URT中可吸收到血流中的母体乙酸乙酯的量。
Nasal tissues contain large amounts of carboxylesterase but its precise role in metabolism of inspired ester vapors is not known. The current study was aimed at quantitating the extent of metabolism of inspired ethyl acetate in the upper respiratory tract (URT) of the F344 rat and Syrian hamster. Ethyl acetate deposition was measured in the surgically isolated URT of these species under constant velocity unidirectional flow conditions. The degree of metabolism was estimated by mathematic modeling based on a simple venous-equilibration approach and by direct comparison of deposition efficiencies in naive and carboxylesterase-inhibited animals. Ethyl acetate deposition efficiencies averaged between 10 and 35% in the rat URT and 36 and 72% in the hamster. Carboxylesterase inhibition decreased deposition in both species. Both the modeling efforts and the direct comparisons between naive and inhibited animals indicated that significant amounts of the deposited ethyl acetate were metabolized in the URT of both species with the extent of metabolism being more pronounced in the hamster. Specifically, 40–65% of the deposited ethyl acetate was metabolized in the URT of the rat compared to 63–90% in the hamster. This first-pass metabolism (i) increased URT deposition efficiencies; (ii) led to production of high metabolite levels in URT tissues; and (iii) decreased the amount of parent ethyl acetate available for absorption into the bloodstream in the URT.