Wills R J, Gallo-Torres H E, Bertko R, Min B H
J Pharmacol Exp Ther. 1987 May;241(2):433-7.
Trimoprostil, a prostaglandin E2 analog, was evaluated to determine if there was a relationship between plasma concentrations and inhibition of histamine-stimulated gastric acid secretion in dogs prepared with Heidenhain pouches. Trimoprostil was given p.o. followed by collection (drainage) of gastric juice from the pouch to determine acid output. In addition, serial blood samples were withdrawn to determine trimoprostil plasma concentrations. Trimoprostil was absorbed rapidly and eliminated with T1/2 ranging from 25 to 37 min. Trimoprostil was effective in inhibiting acid output compared with control. The maximal response and duration of activity were dependent on the concentration-time profile of trimoprostil. Trimoprostil produced a maximum inhibition of 98% and suppressed acid output for at least 3 hr. When plasma concentrations were related to the antisecretory response using a modified Hill equation, the response was found to lag behind plasma concentrations as evidenced by hysteresis loops. The predicted plasma concentration associated with a 50% inhibition of acid secretion (IC50) ranged from 0.58 to 0.79 ng/ml.
曲莫前列素是一种前列腺素E2类似物，对用海登海因小胃制备的犬，评估其血浆浓度与组胺刺激胃酸分泌抑制之间是否存在关联。口服给予曲莫前列素，随后从小胃收集（引流）胃液以测定酸排出量。此外，采集系列血样以测定曲莫前列素的血浆浓度。曲莫前列素吸收迅速，消除半衰期为25至37分钟。与对照组相比，曲莫前列素可有效抑制酸排出量。最大反应和活性持续时间取决于曲莫前列素的浓度 - 时间曲线。曲莫前列素产生的最大抑制率为98%，并至少抑制酸排出量3小时。当使用修正的希尔方程将血浆浓度与抗分泌反应相关联时，发现反应滞后于血浆浓度，滞后环证明了这一点。与50%胃酸分泌抑制（IC50）相关的预测血浆浓度范围为0.58至0.79纳克/毫升。
