Dermal metabolism of 4-nitrophenol and 4-nitroanisole in single-pass perfused rabbit ears.
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 Vmax values for 4-nitrophenol glucuronidation and sulphation were about 20 pmol and 10 pmol/min per cm2, respectively. 4. The difference in apparent Km 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.
Henrikus
B M
BM
Walther-Straub-Institut für Pharmakologie und Toxikologie, Med. Fakultät, Ludwig-Maximilians-Universität, München, Germany.
Breuer
W
W
Kampffmeyer
H G
HG
D000279:Administration, Cutaneous; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000378:metabolism*; D004423:Ear; D005965:Glucuronates / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D066298:In Vitro Techniques; D007261:Infusions, Intra-Arterial; D007700:Kinetics; D009578:Nitrobenzenes / Q000378:metabolism; D009596:Nitrophenols / Q000008:administration & dosage / Q000378:metabolism*; D010477:Perfusion; D011817:Rabbits; D012867:Skin / Q000378:metabolism*
D000840:Anisoles; D005965:Glucuronates; D006001:Glycoconjugates; D009578:Nitrobenzenes; D009596:Nitrophenols; C002730:4-nitrophenylglucuronide; C023379:4-nitrophenyl sulfate; C005306:4-nitroanisole; C024836:4-nitrophenol