title: Metabolism of benzocaine during percutaneous absorption in the hairless guinea pig: acetylbenzocaine formation and activity.
abstract: 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.
authors: Office of Cosmetics and Colors, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, Md 20708, USA.
authors: M E
authors: ME
authors: Kraeling
authors: R J
authors: RJ
authors: Lipicky
authors: R L
authors: RL
authors: Bronaugh
mesh_terms: 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
chemical_list: D000779:Anesthetics, Local; D015221:Potassium Channels; D015222:Sodium Channels; D001566:Benzocaine