Metabolism of ethyl 4-aminobenzoate in the isolated single-pass perfused rabbit ear.

Isolated rabbit ears were single-pass perfused with a protein-free Tris buffer solution. Ethyl 4-amino[U-ring-14C]benzoate or 4-amino[U-ring-14C]benzoic acid was applied to the epithelial surface in isopropyl myristate, or perfused arterially. Metabolites in the effusate were extracted and separated by high-performance liquid chromatography. Five metabolites were separated from ethyl aminobenzoate and identified as aminobenzoic acid, or acid-labile conjugates from either substrate. Their chemical structure has not yet been established. One metabolite, perhaps a glycolic acid N-conjugate of ethyl 4-aminobenzoate, was found at about 100 times higher concentration after arterial than after dermal drug application, indicating that the quantitative metabolic patterns in skin differ depending on whether the xenobiotic reaches the enzymes of the skin by cutaneous absorption or by the blood circulation. The metabolite pattern of the skin was compared with that from rabbit or rat liver cell preparations.