Browse by author
Lookup NU author(s): Dr Christopher Jewell,
Professor Faith Williams
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
The capacity of human, minipig, and rat skin and liver subcellular fractions to hydrolyze the anesthetic ester procaine was compared with carboxylesterase substrates 4-methylumbelliferyl-acetate, phenylvalerate, and para-nitrophenylacetate and the arylesterase substrate phenylacetate. Rates of procaine hydrolysis by minipig and human skin microsomal and cytosolic fractions were similar, with rat displaying higher activity. Loperamide inhibited procaine hydrolysis by human skin, suggesting involvement of human carboxylesterase hCE2. The esterase activity and inhibition profiles in the skin were similar for minipig and human, whereas rat had a higher capacity to metabolize esters and a different inhibition profile. Minipig and human liver and skin esterase activity was inhibited principally by paraoxon and bis-nitrophenyl phosphate, classical carboxylesterase inhibitors. Rat skin and liver esterase activity was inhibited additionally by phenylmethylsulfonyl fluoride and the arylesterase inhibitor mercuric chloride, indicating a different esterase profile. These results have highlighted the potential of skin to hydrolyze procaine following topical application, which possibly limits its pharmacological effect. Skin from minipig used as an animal model for assessing transdermal drug preparations had similar capacity to hydrolyze esters to human skin. Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics.
Author(s): Jewell C, Ackermann C, Payne NA, Fate G, Voorman R, Williams FM
Publication type: Article
Publication status: Published
Journal: Drug Metabolism and Disposition
ISSN (print): 0090-9556
ISSN (electronic): 1521-009X
Publisher: American Society for Pharmacology and Experimental Therapeutics
PubMed id: 17664252
Altmetrics provided by Altmetric