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三甲双酮是评价肝微粒体药物代谢酶功能的一个重要指标。它主要由苯巴比妥类诱导的肝微粒体细胞色素Ｐ４５０亚型代谢。本研究用Ｎ－甲氧基，β－（对－苯酚基甲烷）吡咯烷酮（ＮＭＰＭＰ）作为细胞色素Ｐ４５０诱导剂，测定犬肝微粒体Ｐ４５０总量及Ｐ４５０亚型２Ｂ，３Ａ的含量；同时用肝微粒体重组系统测定Ｐ４５０单加氧酶活力，并用免疫抑制试验确定细胞色素Ｐ４５０亚型，２Ｂ和３Ａ对三甲双酮代谢的影响。结果表明：经Ｎ－ＭＰＭＰ诱导的犬Ｐ４５０，Ｐ４５０２Ｂ和Ｐ４５０３Ａ含量都增加；苄甲苯异丙胺Ｎ－脱甲基和４－硝基甲醚０－脱甲基活力增高；在重组系统，针对犬Ｐ４５０２Ｂ的多克隆抗体可部分抑制三甲双酮和平甲苯异丙胺Ｎ－脱甲基活动。本研究结果提示，就三甲双酮Ｎ－脱甲基活力这一点上，大鼠和犬间差别不大；与三甲双酮代谢有关的Ｐ４５０亚型是Ｐ４５０２Ｂ。
Trimethadione is an important indicator of the function of hepatic microsomal drug metabolizing enzymes. It is mainly metabolized by phenobarbital-induced liver microsomal cytochrome P450 isoforms. In this study, the total amount of canine liver microsome P450 and the content of P450 subtypes 2B, 3A were determined by using N-methoxy and β-p-phenolmethanepyrrolidone (NMPMP) as cytochrome P450 inducer. The activity of P450 monooxygenase was determined by the microsomal recombination system and the effects of cytochrome P450 subtype, 2B and 3A on the metabolism of trimethadione were determined by immunosuppression assay. The results showed that the content of P450, P4502B and P4503A in canine induced by N-MPMP increased; the activity of 0-demethylation of benzylt-isopropylamine N-demethyl and 4-nitro-methyl ether increased; in the recombinant system, Of the polyclonal antibody may partially inhibit the N-demethylation of trimethadione and tamoxifen. The results of this study suggest that there is little difference between N-demethylation of trimethadione and canine; the P450 subtype associated with Metformin metabolism is P4502B.