Journal article
Differential expression of CYP3A12 and CYP3A26 mRNAs in canine liver and intestine
Xenobiotica, Vol.38(10), pp.1305-1312
10/2008
Handle:
https://hdl.handle.net/2376/109644
PMID: 18841518
Abstract
The cytochrome P450 (CYP) 3A family is often considered the most important CYP subfamily with regard to drug metabolism in people. Certainly, CYP3A4 contributes to poor oral bioavailability of a number of drugs, and a tremendous amount of effort has been made in attempting to find an appropriate model system to predict the oral bioavailability of candidate drugs. The dog is a species widely used as a preclinical model for the evaluation of drug safety and pharmacokinetics. Compared with other species, little information is available on the tissue distribution of CYP enzymes. The purpose of this study was to determine the level of messenger RNA (mRNA) expression of the canine CYP3A subfamily (CYP3A12 and CYP3A26) in the liver and duodenum. Overall, expression of CYP3A mRNA was greater in the liver than in the duodenum. Hepatic expression of CYP3A26 was greater than CYP3A12 in all dogs, with CYP3A26 comprising 75.2% of the hepatic mRNA CYP3A pool. Conversely, duodenal expression of CYP3A12 was greater than CYP3A26 in all dogs, with CYP3A12 comprising 99.8% of the duodenal mRNA CYP3A pool. In summary, these results represent an important step toward the systematic comparison of human and canine CYP3A enzymes, particularly in relation to oral bioavailability of substrate drugs.
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Details
- Title
- Differential expression of CYP3A12 and CYP3A26 mRNAs in canine liver and intestine
- Creators
- K. L Mealey - Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USAM Jabbes - Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USAE Spencer - Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USAJ. M Akey - Department of Genome Sciences, University of Washington, Seattle, WA, USA
- Publication Details
- Xenobiotica, Vol.38(10), pp.1305-1312
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- Informa UK Ltd
- Identifiers
- 99900547025401842
- Language
- English
- Resource Type
- Journal article