Ester hydrolysis and conjugation reactions in intact skin and skin homogenate, and by liver esterase of rabbits.
1. Procaine, 2-chloroprocaine, ethyl aminobenzoate and methyl salicylate were added at various concentrations to liver esterase, supernatant of skin homogenate, or single-pass perfused ears of rabbits. 2. Vmax of product formation by purified liver esterase correlated with the rank order of the distribution coefficients (n-octanol/buffer) of the substrates and ranged between 11 and 1100 pmol/min per micrograms protein. Km values were between 20 and 50 microM. 3. No correlation was observed when the apparent enzyme kinetics, calculated by non-linear adaptation, were compared with each other after substrate administration to skin, arterial influx, or incubation with skin homogenate. 4. An acid labile conjugate of ethyl 4-aminobenzoate was found, mainly during arterial perfusion and in supernatant of skin homogenate, after administration of ethyl 4-aminobenzoate. 5. Acetamidobenzoic acid was observed in quantities of about 10% of the free 4-aminobenzoic acid during dermal or arterial application of procaine. This metabolite was not found with ethyl 4-aminobenzoate. 6. The results from isolated rabbit ear perfusion differ quantitatively and qualitatively with those obtained from supernatant of skin homogenate or purified liver esterase.
Henrikus
B M
BM
Walther-Straub-Institut für Pharmakologie und Toxikologie der Med., Fakultät der Ludwig-Maximilians-Universität, München, Germany.
Kampffmeyer
H G
HG
D000779:Anesthetics, Local / Q000493:pharmacokinetics; D000818:Animals; D001566:Benzocaine / Q000737:chemistry / Q000493:pharmacokinetics; D002682:Chinchilla; D002851:Chromatography, High Pressure Liquid; D004950:Esterases / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D010477:Perfusion; D011343:Procaine / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D012867:Skin / Q000737:chemistry* / Q000201:enzymology
D000779:Anesthetics, Local; D004952:Esters; D011343:Procaine; D004950:Esterases; D001566:Benzocaine