Knoll R, Christ W, Müller-Oerlinghausen B, Coper H
Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(2):195-200. doi: 10.1007/BF00499931.
The metabolism of chlorpromazine by microsomal preparations of the small intestine from guinea pig and rat was studied. 35S-chlorpromazine was incubated with these preparations in Krebs-Ringer bicarbonate buffer at 37 degrees C. Control values were obtained by performing the assay at 0 degrees C. The metabolites were extracted with dichloroethane and separated by TLC. In incubations with intestinal microsomes from guinea pigs chlorpromazine sulphoxide and monodesmethyl chlorpromazine were identified as main metabolites. The apparent Michaelis constant for sulphoxidation of chlorpromazine is approximately 20-30 micronM and for N-demethylation in the range of 30-100 micronM. Using microsomal preparations from rat intestine, however, noteworthy formation of chlorpromazine metabolites could not be found. This observation can be explained by the fact that the cytochrome P450 content of rat intestinal microsomes was extremely low compared with that determined in guinea pig microsomes.
研究了氯丙嗪在豚鼠和大鼠小肠微粒体制剂中的代谢情况。将35S - 氯丙嗪与这些制剂在37℃的 Krebs - Ringer碳酸氢盐缓冲液中孵育。通过在0℃进行测定获得对照值。代谢产物用二氯乙烷萃取并通过薄层层析分离。在用豚鼠肠道微粒体孵育时，氯丙嗪亚砜和单去甲基氯丙嗪被鉴定为主要代谢产物。氯丙嗪亚砜化的表观米氏常数约为20 - 30微摩尔，N - 去甲基化的表观米氏常数在30 - 100微摩尔范围内。然而，使用大鼠肠道微粒体制剂时，未发现氯丙嗪代谢产物的显著形成。这一观察结果可以用以下事实来解释，即与豚鼠微粒体中测定的细胞色素P450含量相比，大鼠肠道微粒体中的细胞色素P450含量极低。
