Disease relevance of Leo 271 f

• We have, therefore, examined the level of the four metabolites, estromustine (EoM), estramustine (EaM), estrone, and estradiol in the tumor and serum of 14 patients with T2 and T3 prostate cancer receiving a single i.v. dose of 600 mg of EMP, about 12 h before radical prostatectomy [1].
• The expression of the estramustine/estromustine-binding protein (EMBP) in human mammary cancer and malignant melanoma was examined by immunochemical methods and compared with that in endometrial and ovarian cancers [2].

High impact information on Leo 271 f

• Pharmacokinetics of EMP and the metabolites estramustine (EaM), estromustine (EoM), estradiol, and estrone were assessed after weeks 1 and 4 of treatment [3].
• Estramustine phosphate is metabolically activated in vivo, and its metabolites, estramustine, estromustine, estrone, and beta-estradiol inhibit the assembly of microtubules [for review see: Kreis W, In: Concepts, Mechanisms, and New Targets for Chemotherapy (Ed. Muggia FM), pp. 163-184. Kluwer Academic Publishers, Boston, 1995] [4].
• Using gas chromatography the metabolites of EMP, estramustine (EaM) and estromustine (EoM), were quantified, EMBP was demonstrated by immunohistochemistry [5].
• Uptake studies revealed that estramustine (EM), and its 17-ketoanalogue estromustine (EoM), differed in their nuclear binding pattern in 1013L cells but not in HeLa cells [6].
• In addition, the uptake of EaM and its metabolites estromustine (EoM), estradiol, and estrone were analyzed by gas chromatography [7].

Biological context of Leo 271 f

• In comparison with water, the AUC of estromustine was 41% when the drug was taken with milk and 67% after simultaneous intake of standardized food [8].
• The relative bioavailability of estromustine after administration of EMP-capsules was 44%, which reflects incomplete absorption of EMP rather than first-pass metabolism of estromustine [9].
• The tmax and lag time of estromustine were significantly increased by milk and food intake and Cmax and AUC were significantly decreased [8].
• The interaction of estramustine and estromustine, cytotoxic metabolites of estramustine phosphate (Estracyt), with protein-binding sites in rat pancreatic tissue was examined [10].

Anatomical context of Leo 271 f

• Accumulation of estramustine and estromustine in adipose tissue of rats and humans [11].

Analytical, diagnostic and therapeutic context of Leo 271 f

• As judged by gas chromatography, the concentration of estromustine, which is the main metabolite in man, was about 13 times higher in fat than in plasma and was also higher in adipose tissue than in muscle and liver [11].
• Liquid chromatography verified that the radioactivity represented estramustine and estromustine [11].
• In contrast to estromustine, oestradiol inhibited testicular blood flow, as measured by the microsphere technique [12].

References