CYCLOSPORINE ABSORPTION IS IMPAIRED BY THE FAT SUBSTITUTES, SUCROSE POLYESTER AND TRICARBALLYLATE TRIESTER, IN THE RAT

The effect of non-absorbable fat substitutes (sucrose polyester (SPE) and tricarballylate triester (TCTE)) on cyclosporin A (CsA) intestinal absorption was studied in the rat using in situ perfusion and gastric intubation techniques. A first experiment using the recirculating intestinal perfusion model showed that emulsions of either 5% SPE or TCTE significantly reduced (p < 0.0008) CsA absorption, whereas no difference was found between results for saline and 5% olive oil emulsion. In single-pass intestinal perfusion experiments SPE dose-dependently inhibited CsA absorption at SPE concentrations of 0.31% (p < 0.0004) and higher. Using gastric intubation, whole blood CsA concentrations significantly decreased when administered with SPE and TCTE in comparison with olive oil(p < 0.04). These results confirm that the CsA fraction dissolved in the undigested oil phase, constituted by the undigested and nonabsorbed fat substitute, is unavailable for intestinal absorption.