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大鼠吸入亚硝酸正丁酯的摄取及体内转化

Uptake of inhaled n-butyl nitrite and in vivo transformation in rats.

作者信息

Osterloh J D, Goldfield D

出版信息

J Pharm Sci. 1985 Jul;74(7):780-2. doi: 10.1002/jps.2600740719.

Abstract

The uptake of butyl nitrite by rats (500 g, one rat/chamber) was determined over a 5-min exposure period. About 44% of the starting amount (771-3855 ppm) of n-butyl nitrite was consumed in 5 min. Three rats per exposure concentration were individually studied for 0-150 min after exposure. Concentrations of blood methemoglobin and plasma nitrate, nitrite, butyl nitrite, and butyl alcohol were examined. No free nitrite ion or butyl nitrite was detectable in the plasma at any time (6.5-150 min) following the exposure. Concentrations at 6.5 min of butyl alcohol, nitrate ion, and methemoglobin increased with increasing exposure concentrations. Plasma concentrations of butyl alcohol were detectable only briefly at 6.5 and 20 min. Methemoglobin levels decreased linearly at higher concentrations and as an approximate first-order process at lower concentrations (less than 15 g/L of whole blood). By 20 min after the inhalation period, plasma nitrate concentrations had decreased from peak levels to higher than baseline steady-state nitrate concentrations. Nitrosothiols were not detectable in the plasma protein fraction.

摘要

在5分钟的暴露期内测定了大鼠(500克,每室1只大鼠)对亚硝酸丁酯的摄取量。在5分钟内,约44%的起始量(771 - 3855 ppm)的亚硝酸正丁酯被消耗。对每个暴露浓度的三只大鼠在暴露后0 - 150分钟进行单独研究。检测了血液高铁血红蛋白以及血浆中硝酸盐、亚硝酸盐、亚硝酸丁酯和丁醇的浓度。暴露后的任何时间(6.5 - 150分钟)血浆中均未检测到游离亚硝酸根离子或亚硝酸丁酯。在6.5分钟时,丁醇、硝酸根离子和高铁血红蛋白的浓度随暴露浓度的增加而升高。血浆中丁醇的浓度仅在6.5分钟和20分钟时短暂可检测到。在较高浓度下高铁血红蛋白水平呈线性下降,在较低浓度(全血低于15 g/L)下呈近似一级过程下降。吸入期后20分钟时,血浆硝酸盐浓度已从峰值降至高于基线稳态硝酸盐浓度。血浆蛋白部分未检测到亚硝基硫醇。

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