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 inhibitors, aprotinin, bacitracin, and soybean trypsin inhibitor, on the small and large intestinal absorption of phenol red (PR) and fluorescein isothiocyanate dextrans (FDs) were examined in rats. Of these protease inhibitors, only bacitracin enhanced the absorption of PR and FDs from the rat small and large intestine. Thus, we suggest that bacitracin has not only a protease-inhibitory but also an absorption-enhancing capability. We examined the effects of various protease inhibitors on intestinal mucosal toxicity by measuring the leakage of Evans blue (EB) from the systemic circulation. Although there was a significant increase in the leakage of EB in the presence of bacitracin, it was considerably 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 it did not cause serious intestinal mucosal damage, as seen in the case of BL-9.