Age difference in simultaneous permeation and metabolism of ethyl nicotinate in rat skin

The age-dependent characteristics of transdermal permeation of ethyl nicoti nate (EN) and its metabolism to nicotinic acid (NA) were examined in rats a t the ages of a fetus at 21 d, 3, 10, 50, 270 and 360 d, Skin transport in vitro was investigated using mounted skin in side-by-side diffusion chamber s, and flux of EN and NA was determined. with developing and aging in rats, EN flux from EN-saturated solution declined gradually; however, NA flux in creased drastically at 10 and 50 d, To elucidate the mechanism of this age- dependent escalation of NA flux, a hydrolysis study was performed using ski n homogenate, and the Michaelis-Menten parameters (V-max and K-m) of EN wer e evaluated, V-max and V-max/K-m ratio showed the same tendency with NA flu x/total (EN+NA) nus ratio, suggesting that skin esterases in rats are devel oped gradually after birth, then increase markedly and become steady in the adult period. On the other hand, the affinity parameter, K-m, was almost t he same among all ages. Moreover metabolic saturation of esterase during th e transdermal process occurred in all ages, and maximal NA But and EN conce ntration in the donor compartment for the maximal NA flux were also affecte d by age, These findings indicated that the discrepancy in transdermal prof iles of EN among the ages tested was dominantly due to the difference in th e development of esterase in the growth process.