Olkowski A, Gooneratne R, Eason C
Animal and Veterinary Sciences Group, Lincoln University, Canterbury, New Zealand.
Vet Hum Toxicol. 1998 Aug;40(4):208-12.
A comparative study was conducted of the inhibition of liver microsomal cytochrome P450 phase I biotransformation enzyme activity of the Australian brushtail possum, rat, rabbit, sheep and chicken. The possum has caused considerable agricultural and ecological problems since its introduction to New Zealand. This work investigated species differences in cytochrome P450 inhibition by selected imidazole derivatives that may be exploited for designing a more species-specific method of toxicological control of the New Zealand possum population. The imidazole derivatives used were ketoconazole, clotrimazole, miconazole and cimetidine. The potency of these inhibitors varied, with clotrimazole and miconazole being most potent, followed by ketoconazole. Cimetidine was the least effective inhibitor. The inhibitory effect of imidazole derivatives on cytochrome p450 phase I biotransformation enzymes appeared more effective in the possum than in other species. All inhibitors used produced type II spectra upon interaction with cytochrome P450 preparations. Possum and chicken microsomal preparations showed absorbancy maxima at 428 nm, rabbit and rat and 429 nm, and sheep at 431 nm.
对澳大利亚帚尾袋貂、大鼠、兔子、绵羊和鸡的肝脏微粒体细胞色素P450 I相生物转化酶活性的抑制作用进行了比较研究。自引入新西兰以来，袋貂已造成了相当严重的农业和生态问题。这项研究调查了特定咪唑衍生物对细胞色素P450抑制作用的物种差异，这些差异可用于设计一种更具物种特异性的方法来毒理学控制新西兰袋貂种群。所用的咪唑衍生物为酮康唑、克霉唑、咪康唑和西咪替丁。这些抑制剂的效力各不相同，克霉唑和咪康唑效力最强，其次是酮康唑。西咪替丁是最无效的抑制剂。咪唑衍生物对细胞色素P450 I相生物转化酶的抑制作用在袋貂中似乎比在其他物种中更有效。所有使用的抑制剂与细胞色素P450制剂相互作用时均产生II型光谱。袋貂和鸡的微粒体制剂在428nm处显示最大吸光度，兔子和大鼠在429nm处，绵羊在431nm处。
