METABOLISM OF BENZOCAINE DURING PERCUTANEOUS-ABSORPTION IN THE HAIRLESS GUINEA-PIG - ACETYLBENZOCAINE FORMATION AND ACTIVITY

The effect of dose and enzymatic inhibition on the percutaneous absorp tion and metabolism of benzocaine was studied in vitro in the hairless guinea pig, At the dose level of 2 mu g/cm(2), benzocaine was rapidly absorbed and extensively metabolized (80%) by acetyltransferase. As t he applied dose of benzocaine was increased to 40 and 200 mu g/cm(2), N-acetylation of benzocaine decreased to 44 and 34%, respectively, sug gesting saturation of the acetyltransferase system, Total C-14 absorpt ion after benzocaine application was not significantly different betwe en control and enzyme-inhibited skin and therefore does not appear to be affected by the extent of benzocaine metabolism during percutaneous penetration, Skin provides a significant first-pass metabolic effect for therapeutic doses of percutaneously absorbed benzocaine, and the p rimary metabolite formed, acetylbenzocaine, is biologically active.