Regional difference in intestinal drug absorption as a measure for the potential effect of P-glycoprotein efflux transporters.

OBJECTIVES: The aim of this research was to assess regional difference in the intestinal absorption of ranitidine HCl as an indicator for the potential effect of P-glycoprotein (P-gp) efflux transporters.

METHODS: In situ rabbit intestinal perfusion was used to investigate absorption of ranitidine HCl, a substrate for P-gp efflux from duodenum, jejunum, ileum and colon. This was conducted both in the presence and absence of piperine as P-gp inhibitor.

KEY FINDINGS: Ranitidine HCl was incompletely absorbed from rabbit intestine. The length normalized absorptive clearance (PeA/L) of ranitidine HCl was ranked as colon > duodenum > jejunum > ileum. This is the reverse order of the magnitude of P-gp expression. Coperfusion of piperine with ranitidine HCl significantly increased the PeA/L of ranitidine HCl from jejunum and ileum with no significant change on the absorption from duodenum and colon. This was confirmed by significant reduction in the length required for complete ranitidine HCl absorption from jejunum and ileum in presence piperine.

CONCLUSIONS: The results indicate that P-gp transporters play a major role in determining regional difference in intestinal absorption of ranitidine HCl. Thus, the regional absorption of drugs may be taken as an indirect indication for the role of P-gp in intestinal absorption.