In this article, we will discuss Mitotane (Clinical Pharmacology). So, let’s get started.
Mitotane can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. Its biochemical mechanism of action is unknown. Data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex. The administration of Mitotane alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-β-hydroxycortisol. Data in adrenal carcinoma patients indicate that about 40% of oral Mitotane is absorbed and approximately 10% of administered dose is recovered in the urine as a water-soluble metabolite. A variable amount of metabolite (1 to 17%) is excreted in the bile and the balance is apparently stored in the tissues. Following discontinuation of Mitotane, the plasma terminal half-life has ranged from 18 to 159
days. In most patients blood levels become undetectable after 6 to 9 weeks. Autopsy data have provided evidence that Mitotane is found in most tissues of the body; however, fat tissues are the primary site of storage. Mitotane is converted to a water-soluble metabolite. No unchanged Mitotane has been found in urine or bile.