The absorption, distribution and metabolic fate of danazol in rats, monkeys and human volunteers.

Abstract

The metabolism of danazol has been investigated in the rat, the monkey and in human volunteers using 14C-isoxazolo-, 14C-ethynyl, 6,7-tritiated and unlabelled compound. The drug was well absorbed, and rapidly metabolized; approximately 60 endproducts were seen in monkey urine. Four compounds have been unequivocally identified in monkey fecal extracts by physico-chemical methods; several others have been tentatively identified by chromatographic means. Very little unchanged danazol was found in monkey urine or feces at physiological dosages; the major identified urinary and fecal end-products were 2-hydroxymethylethisterone, delta1-2-hydroxymethylethisterone and ethisterone. In the rat the major portion of the radioactivity was excreted in the fecal matter, while in the monkey about equal portions were eliminated in urine and feces. Tissue distribution studies in monkeys and rats showed concentrations greater than the plasma levels only in the liver, adrenal glands and kidneys.