Awouters F, Niemegeers C J, Lenaerts F M, Janssen P A
J Pharm Pharmacol. 1978 Jan;30(1):41-5. doi: 10.1111/j.2042-7158.1978.tb13150.x.
Forty-four non-steroidal anti-inflammatory compounds were tested for possible effects on castor oil-induced diarrhoea in rats. A small but significant delay of intestinal evacuations was found with all compounds. Quantitatively, the oral doses required to delay diarrhoea beyond the first hour after castor oil challenge reflected the acute anti-inflammatory potency of the tested compounds. Qualitatively, the evolution of the effective doses with increasing delay was linear for potent inhibitors of prostaglandin biosynthesis. The evolution for less potent compounds was markedly different and suggested the earlier occurrence of non-specific drug effects. Suprofen, the most potent of the series of compounds, produced the 1 h delay at an oral dose of 1.11 mg kg-1; the ED50 increased linearly to 115 mg kg-1 for a 4 h delay. Compared with other compounds the activity pattern of suprofen was consistent with that of a very potent, short-acting inhibitor of prostaglandin biosynthesis, which maintains its specific action over a wide dose range. It is concluded that delay of castor oil-induced diarrhoea in rats allows a detailed characterization of aspirin-like compounds, and that inhibition of prostaglandin biosynthesis is insufficient to suppress the intestinal effects of the oil.
对44种非甾体抗炎化合物进行了测试，以研究其对蓖麻油诱导的大鼠腹泻可能产生的影响。发现所有化合物均能使肠道排空出现轻微但显著的延迟。从数量上看，在蓖麻油激发后超过第一小时延迟腹泻所需的口服剂量反映了受试化合物的急性抗炎效力。从质量上看，对于前列腺素生物合成的强效抑制剂，随着延迟时间增加有效剂量的变化呈线性。效力较弱的化合物的变化则明显不同，表明更早出现了非特异性药物效应。该系列化合物中效力最强的舒洛芬，口服剂量为1.11 mg·kg-1时可产生1小时的延迟；延迟4小时时，半数有效剂量（ED50）线性增加至115 mg·kg-1。与其他化合物相比，舒洛芬的活性模式与一种强效、短效的前列腺素生物合成抑制剂一致，该抑制剂在很宽的剂量范围内都能保持其特定作用。得出的结论是，大鼠中蓖麻油诱导的腹泻延迟可对阿司匹林样化合物进行详细表征，并且前列腺素生物合成的抑制不足以抑制蓖麻油对肠道的影响。
