Characterization of cytochrome P450-mediated drug metabolism in cats
Characterization of cytochrome P450-mediated drug metabolism in cats
复制标题
DOI：
10.1111/j.1365-2885.2007.00902.x
复制
发表时间：
2007-10-01
影响因子：
1.3
通讯作者：
Shimoda, M.
中科院分区：
文献类型：
--
作者：
Shah, S. S.;Sanda, S.;Shimoda, M.
在这项研究中，我们使用五只雄性猫和五只雌性猫的肝微粒体检查了细胞色素 P450 (CYP)1A、2C、2D 和 3A 的活性。 CYP1A、2C、2D和3A活性分别通过乙氧基试卤灵O-脱乙基化(EROD)、甲苯磺丁脲羟基化(TBH)、丁呋洛尔1'-羟基化(BLH)以及咪达唑仑1'-和4-羟基化来表示。抗大鼠CYP1A2和CYP3A2血清显着抑制EROD和咪达唑仑1'-和4-羟基化，表明猫体内EROD和咪达唑仑1'-和4-羟基化分别由CYP1A和3A催化。奎尼丁在相当低的浓度下抑制猫微粒体中的 BLH，表明猫中 BLH 是由 CYP2D 催化的。雄性和雌性猫的肝微粒体中甲苯磺丁脲羟基化活性可以忽略不计，表明猫的 CYP2C 活性极低。这表明应谨慎给猫施用 CYP2C 底物。虽然CYP1A活性没有性别差异，但猫的CYP2D和3A活性存在差异。雌性猫的 CYP2D 活性较高（3 倍），但 CYP3A 活性较低（五分之一）。这些结果可能表明，应使用不同的剂量方案为雄性和雌性猫开出 CYP2D 和 3A 底物。
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.