Taylor B M, Sun F F
J Pharm Sci. 1979 Aug;68(8):983-6. doi: 10.1002/jps.2600680817.
The absorption of dinoprost (prostaglandin F2 alpha) and its methyl ester in rat jejunum was studied. A 22-cm segment of rat jejunum was cannulated at both ends and connected to an oscillating perfusion pump system. The mesenteric vasculature supplying this isolated segment also was cannulated and perfused with Kreb's bicarbonate buffer with dextran. Solutions of 3H-dinoprost or its methyl ester were introduced into the lumen and oscillated through the segment. The disappearance of radioactivity from the lumen and the appearance of radioactivity in the vascular perfusate were monitored. The metabolite patterns in the vascular perfusate were analyzed by TLC. A lag between the time the drug disappeared from the lumen and the time it appeared in the mesenteric circulation was detected. This lag was longer for the methyl ester than for the free acid, even though the ester disappears from the lumen faster than does the free acid. Upon removal of dinoprost from the gut lumen, a gradual decrease in the amount of drug appearing in the mesenteric circulation could be detected. However, with the ester, a slight increase could be observed for approximately 0.5 hr, followed by a decrease. Metabolism by the gut wall appears to be greater for the ester than for the acid. The results suggest that, although the ester disappears from the lumen more quickly than does the acid, it actually penetrates to the blood at a slower rate and undergoes greater metabolism.
研究了地诺前列素（前列腺素F2α）及其甲酯在大鼠空肠中的吸收情况。将一段22厘米长的大鼠空肠两端插管，并连接到一个振荡灌注泵系统。供应这个分离段的肠系膜血管系统也进行插管，并灌注含有右旋糖酐的克雷布斯碳酸氢盐缓冲液。将3H-地诺前列素或其甲酯溶液引入肠腔，并使其在该段中振荡。监测肠腔中放射性的消失以及血管灌注液中放射性的出现。通过薄层层析分析血管灌注液中的代谢物模式。检测到药物从肠腔消失的时间与它出现在肠系膜循环中的时间之间存在延迟。甲酯的这种延迟比游离酸更长，尽管甲酯从肠腔中消失的速度比游离酸更快。从肠腔中去除地诺前列素后，可以检测到出现在肠系膜循环中的药物量逐渐减少。然而，对于甲酯，在大约0.5小时内可以观察到轻微增加，随后减少。肠壁对甲酯的代谢似乎比对酸的代谢更大。结果表明，尽管甲酯比酸从肠腔中消失得更快，但它实际上进入血液的速度较慢，并且经历更大程度的代谢。
