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 absorption and metabolism of benzocaine was studied in vitro in the hairless guinea pig. At the dose level of 2 micrograms/cm2, benzocaine was rapidly absorbed and extensively metabolized (80%) by acetyltransferase. As the applied dose of benzocaine was increased to 40 and 200 micrograms/cm2, N-acetylation of benzocaine decreased to 44 and 34%, respectively, suggesting saturation of the acetyltransferase system. Total 14C absorption after benzocaine application was not significantly different between 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 primary metabolite formed, acetylbenzocaine, is biologically active.
Kraeling
M E
ME
Office of Cosmetics and Colors, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, Md 20708, USA.
Lipicky
R J
RJ
Bronaugh
R L
RL
D000107:Acetylation; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001566:Benzocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics; D049832:Decapodiformes; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects
D000779:Anesthetics, Local; D015221:Potassium Channels; D015222:Sodium Channels; D001566:Benzocaine