Nakamura J, Katayama M, Nishida K, Sasaki H
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Chem Pharm Bull (Tokyo). 1992 Mar;40(3):815-8. doi: 10.1248/cpb.40.815.
An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with salicylic acid, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased compared with the control. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with salicylic acid orally. The blood concentration of SAMG after the intravenous administration of SAM was not increased compared with the control. We suggest that the change in the intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral pretreatment with salicylic acid. The measurement of SAM metabolites may be of value in the assessment of intestinal mucosal damage in vivo.
通过测定水杨酰胺(SAM)的代谢来评估水杨酸在兔肠道中诱导的体内黏膜损伤。使用带有完整肠系膜静脉血收集装置的原位肠囊研究了SAM的肠道首过代谢。通过插管暴露肠道的肠系膜静脉并收集从吸收区域引流的所有静脉血,直接测定SAM及其代谢产物进入肠系膜静脉血的情况。水杨酸口服预处理后,肠系膜静脉血中SAM葡萄糖醛酸苷(SAMG)的出现与对照组相比显著增加。在口服水杨酸预处理的兔子体内,十二指肠内给药SAM后观察到SAMG的血药浓度升高。静脉注射SAM后,SAMG的血药浓度与对照组相比没有增加。我们认为,SAM肠道首过代谢的变化可能是由于水杨酸口服预处理诱导的肠道黏膜损伤所致。SAM代谢产物的测定可能对体内肠道黏膜损伤的评估有价值。