DESCRIPTION
LYSODREN® (mitotane tablets, USP) is an oral chemotherapeutic agent. It is best known by its trivial name, o,p′-DDD, and is chemically, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane. The chemical structure is shown below:
LYSODREN is a white granular solid composed of clear colorless crystals. It is tasteless and has a slight pleasant aromatic odor. It is soluble in ethanol, isooctane, and carbon tetrachloride. It has a molecular weight of 320.05.
Inactive ingredients in LYSODREN tablets are: avicel, Polyethylene Glycol 3350, silicon dioxide, and starch.
LYSODREN is available as 500 mg scored tablets for oral administration.
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CLINICAL PHARMACOLOGY
LYSODREN 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 LYSODREN 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 LYSODREN is absorbed and approximately 10% of the administered dose is recovered in the urine as a water-soluble metabolite. A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues.
Following discontinuation of LYSODREN, 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 LYSODREN is found in most tissues of the body; however, fat tissues are the primary site of storage. LYSODREN is converted to a water-soluble metabolite.
No unchanged LYSODREN has been found in urine or bile.
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