Implications of hepatic cytochrome P450-related biotransformation processes in veterinary sciences.
Cytochrome P450 enzymes (CYP450) represent a superfamily of monooxigenases that play a pivotal role in drug metabolism. In contrast to the extensive database available for human and rodent CYP450 enzyme activities, the data related to animal species that are regular patients in veterinary medicine, are far from being complete. The major obstacles are the significant inter-species and intra-species differences. With the aim to provide an overview of the current knowledge, key data for important species, such as dogs and cats, horses, pigs and ruminants, are presented, and compared with findings from humans. Analysis of these data shows, that currently no links can be established between certain physiological traits, such as herbivorous and carnivorous species, monogastric animal and ruminants, nor within a given species, as for example cattle. This implies that for all new pharmaceutical entities individual assays are needed for every animal species or even every individual breed. It can be anticipated, however, that investigations into the upstream transcriptional regulation of CYP450 enzymes will provide more insight into the observed expression levels, thus allowing to modulate kinetic parameters of old and new drugs, as the same transcription factors control also the expression of prominent drug transporters.
Fink-Gremmels
Johanna
J
Utrecht University, Faculty of Veterinary Medicine, Div. Veterinary Pharmacology, Pharmacy and Toxicology, Yalelaan 104, PO Box 80.152, 3508 TD Utrecht, The Netherlands. J.Fink@uu.nl
D000818:Animals; D015415:Biomarkers; D001711:Biotransformation; D002415:Cats; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004285:Dogs; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000378:metabolism; D006736:Horses; D008099:Liver / Q000201:enzymology*; D011110:Polymorphism, Genetic; D012418:Ruminants; D013045:Species Specificity; D013552:Swine; D019155:Veterinary Drugs / Q000378:metabolism*
D015415:Biomarkers; D004785:Environmental Pollutants; D019155:Veterinary Drugs; D003577:Cytochrome P-450 Enzyme System