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Interspecies variation in the metabolism of zoniporide by aldehyde oxidase.
MedLine Citation:
PMID:  23046389     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
1. Aldehyde oxidase (AO) is a cytosolic enzyme that contributes to the Phase I metabolism of xenobiotics in human and preclinical species. 2. Current studies explored in vitro metabolism of zoniporide in various animal species and humans using S9 fractions. The animal species included commonly used pharmacology and toxicology models and domestic animals such as the cat, cow or bull, pig and horse. 3. In addition, gender and strain differences in some species were also explored. 4. All animals except the dog and cat converted zoniporide to 2-oxozoniporide (M1). 5. Michael-Menten kinetic studies were conducted in species that turned over zoniporide to M1. 6. Marked differences in K(M), V(max) and Cl(int) were observed in the oxidation of zoniporide. 7. Although the K(M) and V(max) of zoniporide oxidation in male and female human S9 was similar, some gender difference was observed in animals especially, in V(max). 8. The domestic animals also showed marked species differences in the AO activity and affinity toward zoniporide.
Authors:
Deepak Dalvie; Cathie Xiang; Ping Kang; Sue Zhou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  -     ISSN:  1366-5928     ISO Abbreviation:  Xenobiotica     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development , La Jolla, CA 92121 , USA.
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