De Luca A, Murray G, Coupar I M
Unit of Addictive Drug Research, School of Pharmaceutical Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
J Pharm Pharmacol. 1993 Dec;45(12):1082-4. doi: 10.1111/j.2042-7158.1993.tb07185.x.
The opiate antidiarrhoeal drugs loperamide (0.6 mg kg-1, i.p.) or difenoxin (0.77 mg kg-1, s.c.), were administered in an anaesthetic mixture (pentobarbitone 60 mg kg-1) to rats. A length of jejunum (approx. 30 cm) was cannulated, washed and then perfused with iso-osmotic saline for 20 min. The perfusion commenced 50 min after drug administration and continued for 20 min. The perfusates were collected for analysis of fluid transport rates and antidiarrhoeal drug content. These doses of the antidiarrhoeals caused marked inhibition of intestinal fluid secretion induced by intra-arterial infusion of vasoactive intestinal peptide. However, neither of the antidiarrhoeal drugs were detected in the intestinal perfusates (< 0.5 ng by HPLC). The results indicate that loperamide and difenoxin have a different pharmacokinetic profile compared with that previously found for morphine under the same conditions.
将阿片类止泻药洛哌丁胺（0.6毫克/千克，腹腔注射）或地芬诺辛（0.77毫克/千克，皮下注射）与麻醉混合物（戊巴比妥60毫克/千克）一起给予大鼠。截取一段空肠（约30厘米），插管、冲洗，然后用等渗盐水灌注20分钟。给药50分钟后开始灌注，并持续20分钟。收集灌注液以分析液体转运速率和止泻药含量。这些剂量的止泻药显著抑制了动脉内输注血管活性肠肽诱导的肠液分泌。然而，在肠灌注液中未检测到任何一种止泻药（高效液相色谱法检测<0.5纳克）。结果表明，与之前在相同条件下对吗啡的研究结果相比，洛哌丁胺和地芬诺辛具有不同的药代动力学特征。
