Role of P-glycoprotein as a secretory mechanism in quinidine absorption from rat small intestine

Journal of Pharmaceutical Sciences
Y EmiT Kimura

Abstract

The intestinal transport of quinidine was characterized in rat small intestine, using the Ussing-type chamber under short-circuited conditions. In the short-circuited condition, quinidine transport was predominantly secretory and the transport rate in jejunum was 3.5 times larger in the secretory direction than that in the absorptive direction. The secretion of quinidine was found to be dependent upon its concentration and to be via a carrier-mediated system in both jejunum and ileum. Although the kinetic characteristic of the carrier-mediated secretion of quinidine was very similar in jejunum and ileum, its contribution was much greater in jejunum because of a higher passive diffusion component in ileum. The secretion of quinidine, well-known as an inhibitor of P-glycoprotein, was inhibited significantly and its absorption was enhanced significantly by several substrates of P-glycoprotein including verapamil, diltiazem, and digitoxin in jejunum. These phenomena were also observed by the addition of 2,4-dinitrophenol. Furthermore, the voltage-clamp studies indicated that the inhibition of quinidine secretion occurred in the transcellular pathway. On the other hand, neither tetraethylammonium nor p-aminohippuric acid affected th...Continue Reading

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