EFFECTS OF PROTEASE INHIBITORS ON THE ABSORPTION OF PHENOL RED AND FLUORESCEIN ISOTHIOCYANATE DEXTRANS FROM THE RAT INTESTINE

The absorption enhancement effects of three types of protease inhibito rs, aprotinin, bacitracin, and soybean trypsin inhibitor, on the small and large intestinal absorption of phenol red (PR) and fluorescein is othiocyanate dextrans (FDs) were examined in rats. Of these protease i nhibitors, only bacitracin enhanced the absorption of PR and FDs from the rat small and large intestine. Thus, we suggest that bacitracin ha s not only a protease-inhibitory but also an absorption-enhancing capa bility. We examined the effects of various protease inhibitors on inte stinal mucosal toxicity by measuring the leakage of Evans blue (EB) fr om the systemic circulation. Although there was a significant increase in the leakage of EB in the presence of bacitracin, it was considerab ly less than that in the case of polyoxyethylene 9-lauryl ether (BL-9) , which was used as a positive control. Therefore, bacitracin may be a good model adjuvant for improving the intestinal absorption of poorly absorbable drugs because a did not cause serious intestinal mucosal d amage, as seen in the case of BL-9.