ESTRAMUSTINE PHOSPHATE - PLASMA-CONCENTRATIONS OF ITS METABOLITES FOLLOWING ORAL-ADMINISTRATION TO MAN, RAT AND DOG

  • 1 January 1980
    • journal article
    • research article
    • Vol. 27  (1) , 17-29
Abstract
Estramustine phosphate, a nitrogen mustard derivative of estradiol used for the treatment of advanced prostatic cancer, was administered orally to man, rat and dog and the plasma concentrations of its unconjugated metabolites were determined by high performance liquid chromatography. In all species the drug was rapidly and completely dephosphorylated prior to reaching the peripheral circulation. In man and the rat, the 17-keto analog of estramustine (estromustine) was the major metabolite found in plasma with considerably lesser amounts of estramustine itself. In the dog, significant concentrations of estramustine and estromustine were present. Highly elevated levels of estrone and estradiol, as a result of cleavage of the nitrogen mustard from the steroid, were observed in all species. Chronic administration of the therapeutic doses of estramustine phosphate to man did not result in any apparent accumulation of circulating metabolites. The metabolite, estromustine, in addition to estramustine, may play an important role in the therapeutic efficacy of estramustine phosphate.