Priymenko N, Ferre J P, Rascol A, Costes G, Toutain P L
Ecole Nationale Vétérinaire de Toulouse, Laboratoire Associé Inra de Physiopathologie et Toxicologie Expérimentales, France.
J Pharmacol Exp Ther. 1993 Dec;267(3):1161-7.
The role of the migrating motor complex (MMC) of the small intestine in the absorption of an enterally administered marker (tolfenamic acid, TA) used to investigate enterohepatic recycling was studied in the fasted dog. TA was rapidly and extensively absorbed in the duodenum as well as in the ileum. In contrast, the conjugated form of TA (CTA) was not absorbed in the duodenum but only in the ileum, i.e., after bacterial hydrolysis. By administering CTA in the duodenum at different phases (I and II) of the MMC, it was shown that CTA had to be propelled from the duodenum to the ileum by the motor activity of the MMC. Under these conditions, the peak plasma TA concentration was only observed when phase II of the MMC present in the duodenum at the time of CTA administration arrived in the ileum. The estimated mean transit time of CTA from the duodenum to ileum was 45 min and the mean hydrolysis time of CTA to TA was about 75 min. It was concluded that 1) in the fasted dog, a relatively long delay must exist between bile excretion of a conjugate and the reabsorption of its free moiety in the ileum and 2) a realistic physiological model of enterohepatic recycling must take into account the MMC pattern of the intestine when drugs are administered to animals in the fasted state.
在禁食的犬体内研究了小肠移行性复合运动（MMC）在用于研究肠肝循环的肠内给药标记物（托芬那酸，TA）吸收中的作用。TA在十二指肠和回肠中均被快速且大量吸收。相比之下，TA的结合形式（CTA）在十二指肠中不被吸收，仅在回肠中被吸收，即在细菌水解之后。通过在MMC的不同阶段（I和II）于十二指肠给予CTA，结果表明CTA必须通过MMC的运动活性从十二指肠推进至回肠。在这些条件下，仅当给予CTA时十二指肠中存在的MMC的II期到达回肠时，才观察到血浆TA浓度峰值。CTA从十二指肠至回肠的估计平均转运时间为45分钟，CTA水解为TA的平均时间约为75分钟。得出的结论是：1）在禁食的犬体内，结合物经胆汁排泄与其游离部分在回肠中的重吸收之间必然存在相对较长的延迟；2）当在禁食状态下给动物给药时，肠肝循环的实际生理模型必须考虑肠道的MMC模式。
