Comparison of skin transport and metabolism of ethyl nicotinate in various species.

The skin transport and metabolism characteristics of ethyl nicotinate (EN) in rabbit, rat, guinea-pig, pig, shed snake skin and human were compared. In vitro skin transport using excised skin and hydrolysis experiments using skin homogenate were carried out. Flux of EN, a metabolite, nicotinic acid (NA), and the total (EN + NA), as well as kinetic parameters (V(max) and K(m)) for hydrolysis of EN were determined and compared among various species. The enzymatic conversion of EN to NA was observed for all skin permeation experiments. Total flux from EN-saturated solution between rabbit, rat, guinea-pig and human was significantly different (P < 0.05). A great difference between species was observed in skin esterase activity. The NA/total flux ratio of human was significantly lower than that of rabbit, rat or guinea-pig but lower than that of shed snake skin (P < 0.05). There is no significant difference in skin permeation and metabolism between human and pig (P > 0.05). Total flux increased linearly with an increase in EN donor concentration for all species. For pig, shed snake skin and human, NA flux increased with an increase in EN donor concentration and reached a plateau, suggesting the metabolic saturation was taking place in the skin. NA flux at plateau and EN donor concentration in which the NA flux reached a plateau were also affected by species difference. These findings indicated that the discrepancy in transdermal profiles of EN among species tested was predominantly due to the difference in the esterase activity in the skin.