Characterization of cytochrome P450-mediated drug metabolism in cats.
In this study we examined activities of cytochrome P450 (CYP)1A, 2C, 2D and 3A using hepatic microsomes from five male and five female cats. CYP1A, 2C, 2D and 3A activities were referred by ethoxyresorufin O-deethylation (EROD), tolbutamide hydroxylation (TBH), bufuralol 1'-hydroxylation (BLH) and midazolam 1'- and 4-hydroxylation respectively. The anti-rat CYP1A2 and CYP3A2 serum significantly inhibited EROD and midazolam 1'- and 4-hydroxylation, suggesting that EROD and midazolam 1'- and 4-hydroxylation were catalysed by CYP1A and 3A in cats respectively. Quinidine inhibited BLH in cats microsomes at quite low concentrations, suggesting that BLH was catalysed by CYP2D in cats. Tolbutamide hydroxylation activities were negligible in hepatic microsomes from both male and female cats, suggesting CYP2C activities of cats are extremely low. This suggests that CYP2C substrates should be carefully administered to cats. Although there is no sexual difference in CYP1A activities, there are differences in CYP2D and 3A activities of cats. CYP2D activities were higher (3-fold), but CYP3A activities were lower (one-fifth) in female cats. These results might suggest that CYP2D and 3A substrates should be prescribed for male and female cats using different dosage regimen.
Shah
S S
SS
Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
Sanda
S
S
Regmi
N L
NL
Sasaki
K
K
Shimoda
M
M
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D002415:Cats / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D006993:Hypnotics and Sedatives / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008874:Midazolam / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism; D014044:Tolbutamide / Q000378:metabolism