Buccal absorption. III. Simultaneous diffusion and metabolism of an aminopeptidase substrate in the hamster cheek pouch

The simultaneous diffusion and metabolism of the D- and L-isomers of the aminopeptidase substrate, leucine-p-nitroanilide (LPNA), were examined in vitro in the hamster cheek pouch. L-LPNA was completely hydrolyzed during diffusion across the cheek pouch, whereas D-LPNA crossed the cheek pouch intact. The metabolic barrier appeared to be localized in the epithelium of the cheek pouch. Addition of an aminopeptidase inhibitor, bestatin, to both diffusion cell reservoirs resulted in decreased hydrolysis of L-LPNA. The experimental results were analyzed with a mathematical model which was developed to describe the simultaneous diffusion and metabolism processes. Using this model it was estimated that the rate of diffusion of L-LPNA across the cheek pouch was less than the capacity of the tissue to hydrolyze L-LPNA.