Dermal metabolism of 4-nitrophenol and 4-nitroanisole in single-pass perfused rabbit ears

Abstract

1. 4-Nitrophenol and 4-nitroanisole were applied either dermally or arterially to isolated rabbit ears perfused under single-pass conditions with protein-free buffer solution.

2. 4-Nitroanisole yielded only phase II metabolites of 4-nitrophenol.

3. The apparent V_max values for 4-nitrophenol glucuronidation and sulphation were about 20 pmol and 10 pmol/min per cm², respectively.

4. The difference in apparent K_m between dermal and arterial drug application is a measure of first-pass metabolism by the epidermal layer.

5. The amount of 4-nitrophenyl conjugate detected after 4-nitroanisole administration was assumed to represent O-dealkylation of 4-nitroanisole; the capacity of this reaction was one order of magnitude lower than the direct conjugation of 4-nitrophenol.