STUDY OF THE ABSORPTION SITE OF CIMETIDINE

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The optimal absorption site of cimetidine was assessed in rats. The ileac pH value (measured by a pH meter with a micro pH combination electrode) was slightly higher than that in other intestinal sites, and the absorption rate constant (k_a) following the administration of cimetidine into the ligated ileac loop was larger than that in the ligated duodenal and jejunal loops. It is suggested that the ileum is the optimal absorption site of cimetidine. On administration of cimetidine into the ligated and unligated intestines, the k_a values of either the duodenum or the ileum were found to be almost the same between the ligated and unligated cases. However, the k_a value of the jejunum in the unligated case was slightly larger than that in the ligated case. Thus, it is suggested that cimetidine is completely absorbed in the duodenum and ileum during its passage through these intestinal sites, but at the jejunum an unabsorbed fraction of cimetidine passes to the ileum, where it is absorbed completely. Based on these results, a pharmacokinetic model for the absorption of cimetidine following oral administration was designed, in which gastric, duodenal, jejunal, and ileac compartments were included separately but enterohepatic circulation was not included, because the biliary excretion of cimetidine following intravenous and oral administrations were generally lower than 2% of the dose. The value of k_<41> was ca. 4 times larger than that of k_<45>, and the value of k_<45> could be approximated to zero in the model.
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STUDY OF THE ABSORPTION SITE OF CIMETIDINE

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