Struck R F, Kari P, Kalin J, Montgomery J A, Marinello A J, Love J, Bansal S K, Gurtoo H L
Biochem Biophys Res Commun. 1984 Apr 30;120(2):390-6. doi: 10.1016/0006-291x(84)91266-x.
Incubation of [3H]-sidechain-labeled and [14C]-C(4)-ring-labeled cyclophosphamide (CPA) with purified cytochrome P-450 from liver microsomes of rats treated with phenobarbital resulted in the production of a major metabolite that contained both labels, was unaffected by diazomethane, possessed high polarity, was identical in TLC and HPLC behavior to a synthetic standard, didechlorodihydroxy -CPA, and was converted to CPA and bis(2-chloroethyl)amine by thionyl chloride . These results indicate that phenobarbital-inducible cytochrome P-450 is able to dechlorinate CPA and may account, in part, for the inability of phenobarbital to enhance the therapeutic activity and toxicity of this important anticancer and immunosuppressive agent.
将[3H]侧链标记和[14C]-C(4)环标记的环磷酰胺（CPA）与用苯巴比妥处理的大鼠肝脏微粒体中的纯化细胞色素P-450一起温育，产生了一种主要代谢物，该代谢物含有两种标记，不受重氮甲烷影响，具有高极性，在薄层色谱（TLC）和高效液相色谱（HPLC）行为上与合成标准品二氯二羟基-CPA相同，并且可通过亚硫酰氯转化为CPA和双（2-氯乙基）胺。这些结果表明，苯巴比妥诱导的细胞色素P-450能够使CPA脱氯，这可能部分解释了苯巴比妥无法增强这种重要抗癌和免疫抑制剂的治疗活性及毒性的原因。
