Date of Defense

Fall 12-1-1992

Department

Biological Sciences

First Advisor

Mary J. Ruwart, Upjohn Company

Second Advisor

Leonard Ginsberg, Biological Sciences

Third Advisor

Stephen Friendmann, Biological Sciences

Abstract

This in situ study was conducted with the intent to resolve the discrepancy found in Rop et al.'s (1992) rat intestinal perfusion study. Rop et al.'s (1992) results showed a substantial lumenal peptide uptake, but reported an almost insignificant amount of peptide found in the mesenteric vein collection sample. This disappearance-reappearance differential was found to be an artifact, and was rectified. Following intestinal perfusion results showed no peptide absorption was occurring with compounds U-88272 and U-88937. The introduction of verapramil to block the multi-drug resistance pump, P-glycoprotein, and facilitate peptide uptake again resulted in no intestinal absorption of U-88272. These results do not correspond with those predicted by heptane-ethylene glycol partition coefficients and Caco-2 permeabilities (Conradi, et al., 1991). Further studies must be conducted to determine the cause for poor peptide absorption, and why results did not concur with the heptane-ethylene glycol and Caco-2 predictions in this specific case.

Access Setting

Honors Thesis-Campus Only

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