Touitou Y, Bogdan A, Legrand J C, Desgrez P
Ann Endocrinol (Paris). 1977;38(1):13-25.
The metabolism of o,p'-DDD (mitotane), a well-known inhibitor of adrenal steroidogenesis in man and animal, is reviewed. Following oral administration, about 65% of the ingested drug were found to pass in the stool. The drug appeared in the urine in metabolized forms: o,p'-DDA and mono-and dihydroxylated derivatives of o.p'-DDA. These latters were found as well in the stools. An unsaturated metabolite, o,p'-DDE was described in plasma and tissues in man. Serum specimens of treated patients were analyzed for o,p'-DDD during various phases of therapy: the levels and the rate of rise during treatment were very variable (5 to 90 microng/ml). Tissue levels were obtained from animals (rats, dogs) or men (biopsy as well as autopsy): o,p'-DDD was primarily found stored in adipose tissue and fat-containing tissues, essentially adrenals. Practical conclusions can be drawn from these results: there is no correlation between the dose of o,p'-DDD administered and its blood level; there is no correlation between blood levels and the patient's responsiveness to the drug; there is a possibility that the molecule transformed in an active metabolite through its metabolism.
本文综述了o,p'-滴滴滴（米托坦）的代谢情况，它是一种在人和动物中广为人知的肾上腺类固醇生成抑制剂。口服给药后，约65%摄入的药物经粪便排出。药物以代谢产物形式出现在尿液中：o,p'-二氯二苯乙酸（o,p'-DDA）以及o,p'-DDA的单羟基和二羟基衍生物。后者在粪便中也有发现。在人体的血浆和组织中发现了一种不饱和代谢产物o,p'-滴滴伊（o,p'-DDE）。在治疗的不同阶段对接受治疗患者的血清样本进行了o,p'-滴滴滴分析：治疗期间的水平和上升速率变化很大（5至90微克/毫升）。组织水平取自动物（大鼠、狗）或人（活检以及尸检）：o,p'-滴滴滴主要储存在脂肪组织和含脂肪组织中，主要是肾上腺。从这些结果可以得出实际结论：给予的o,p'-滴滴滴剂量与其血液水平之间没有相关性；血液水平与患者对药物的反应性之间没有相关性；该分子有可能通过代谢转化为活性代谢产物。
