EFFECT OF METOCLOPRAMIDE ON THE ABSORPTION OF CIMETIDINE IN RATS

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Metoclopramide was found to increase the absorption rate constant (k_a) of cimetidine by the duodenum and jejunum in both ligated and unligated rats. The increase of k_a of cimetidine in the ligated rats cannot be interpreted in terms of an increase in the gastric emptying rate, which has been suggested to be the main effect of metoclopramide. The pH values of the stomach, duodenum and jejunum increased following the administration of metoclopramide. Atropine also increased the pH value of the duodenum, but it did not increase the k_a of cimetidine. Consequently, the increase of k_a of cimetidine, following administration of metoclopramide, was not due to the elevation of intestinal pH. On the other hand, metoclopramide significantly increased the blood flow by about 67.3 and 29.7% at the duodenum and jejunum, respectively, when the intestinal blood flow was measured by the hydrogen clearance method. Attopine had no effect on the intestinal blood flow. Based on these results, it was concluded that the increase of intestinal blood flow may be one of the factors for the increase of k_a of cimetidine following the administration of metoclopramide. From the results of multi-line fittings of the plasma concentration data following oral, intraduodenal, intrajejunal and intraileac administrations of cimetidine with metoclopramide treatment, it was suggested that metoclopramide increased the intestinal transit time of subsequently administered drugs, as well as the gastric emptying rate.
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EFFECT OF METOCLOPRAMIDE ON THE ABSORPTION OF CIMETIDINE IN RATS

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