Kleiman-Wexler R L, Adair C G, Ephgrave K S
College of Pharmacy, University of Iowa, Iowa City.
J Pharmacol Exp Ther. 1989 Nov;251(2):435-8.
The purpose of this study was to determine if the beneficial effect of naloxone on formation of acute gastric mucosal lesions was brought about via central or peripheral mechanisms by measuring blood concentrations of naloxone in rats during a 4-hr period of restraint stress. The study involved administration of naloxone to rats at doses of 5, 20 and 40 mg.kg-1.hr by either the intravenous or enteral routes. Blood samples were collected throughout the period of restraint and gastric stress-lesions were counted at the end of the experiments. Both routes of administration were equally effective in preventing stress-ulceration, with only rats receiving drug intravenously showing the presence of naloxone in blood samples. Inverse linear relationships existed between mean trough blood concentrations and lesions (P = .0003), as well as a linear correlation between area under the time-concentration curve and mean trough concentrations (P = .0001). Although our results show tight correlation between blood levels and effect on lesions in the group given drug intravenously, the effect must be on peripheral rather than central opiate receptors as no detectable blood levels were found when naloxone was given enterally.
本研究的目的是通过在4小时的束缚应激期间测量大鼠体内纳洛酮的血药浓度，来确定纳洛酮对急性胃黏膜损伤形成的有益作用是通过中枢还是外周机制实现的。该研究涉及以5、20和40 mg·kg⁻¹·hr的剂量通过静脉或肠内途径给大鼠注射纳洛酮。在整个束缚期间采集血样，并在实验结束时对胃应激性损伤进行计数。两种给药途径在预防应激性溃疡方面同样有效，只有静脉注射药物的大鼠血样中检测到纳洛酮的存在。平均谷血浓度与损伤之间存在负线性关系（P = 0.0003），时间-浓度曲线下面积与平均谷浓度之间存在线性相关性（P = 0.0001）。虽然我们的结果显示静脉给药组的血药水平与对损伤的影响之间存在紧密相关性，但这种作用一定是在外周而非中枢阿片受体上，因为肠内给予纳洛酮时未检测到可测的血药水平。
