Metabolism of o,p'-DDD (mitotane) in human and animals. Actual notions and practical deductions (author's transl)]

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.