The tissue distribution of estramustine and estromustine, two cytotoxic lipophilic metabolites of estramustine phosphate (Estracyt, EMP) was studied in rats and humans. A single dose of [3H]-estramustine was given i. v. to groups of rats. At 24 h after administration, the concentration of radioactivity in fat was about 20, 12, and 2 times that in muscle, plasma, and liver, respectively. Liquid chromatography verified that the radioactivity represented estramustine and estromustine. The clinical relevance of these results was investigated in pancreas cancer treated with a single oral dose of Estracyt at 12–16 h before surgery. 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. After 5 days of Estracyt treatment, the adipose uptake of estromustine was even higher, namely, about 40 times that in plasma and 8 times that in muscle and liver. Thus, our results demonstrate that estramustine and estromustine are stored in adipose tissue after the administration of EMP; this is important for the pharmacokinetics and, consequently for the therapeutic effects of Estracyt.
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Andersson S-B, Lundgren R, Svensson L (1982) Gas chromatographic determinations in four metabolites of estramustine phosphate in plasma. Acta Pharm Suec 19: 1–10
Bickel MH (1984) The role of adipose tissue in the distribution and storage of drugs. Prog Drug Res 28: 273–303
Forsgren B, Gustafsson J-Å, Pousette Å, Högberg B (1979) Binding characteristics of a major protein in rat ventral prostate cytosol that interacts with estramustine, a nitrogen mustard derivative of 17-β-estradiol. Cancer Res 39: 5155
Gunnarsson PO, Andersson S-B, Johansson S-Å, Nilsson T, Plym-Forshell G (1984) Pharmacokinetics of estramustine phosphate (Estracyt) in prostatic cancer patients. Eur J Clin Pharmacol 26: 113–119
Hartley-Asp B (1984) Estramustine induced mitotic arrest in two human prostatic carcinoma cell lines DU 145 and PC-3. Prostate 5: 93–100
Hartley-Asp B, Gunnarsson PO (1982) Growth and cell survival following treatment with estramustine, nor-nitrogen mustard, estradiol and testosterone of a human prostatic cancer cell line (DU 145). J Urol 127: 818
Hedlund PO (1987) Estracyt — mode of action and clinical experience. In: Prostate cancer, part B: Imaging techniques, radiotherapy, chemotherapy and management issues. Alan R. Liss, New York, pp 215–219
Höisaeter PÅ, Bakke A (1983) Estramustine phosphate (Estracyt): experimental and clinical studies in Europe. Semin Oncol 10 [Suppl 3]: 27–33
Kruse E, Johansson S-Å, Hartley-Asp B, Gunnarsson PO (1988) Distribution and metabolism of estramustine in HeLa cells and the human prostatic tumour cell line 1013L. Biochem Pharmacol 16: 3161–3167
Longcope C, Williams KIH (1974) The metabolism of estrogens in normal women after pulse injections of [3H]-estradiol and [3H]-estrone. J Clin endocrinol 38: 602–607
Norlén BJ, Andersson S-B, Björk P, Gunnarsson PO, Fritjofsson Å (1988) Uptake of estramustine phosphate (Estracyt) metabolites in prostatic cancer. J Urol 140: 1058–1062
Petrov V, Padilla GM (1986) Design of cytotoxic steroids for prostatic cancer. Prostate 9: 169–182
Sörgel F, Jaehde U, Naber K, Stephan U (1989) Pharmacokinetic disposition of quinolones in human body fluids and tissues. Clin Pharmacokinet 16: 5–24
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Gunnarsson, P.O., Andersson, S., Sandberg, Å.A. et al. Accumulation of estramustine and estromustine in adipose tissue of rats and humans. Cancer Chemother. Pharmacol. 28, 361–364 (1991). https://doi.org/10.1007/BF00685690
- Liquid Chromatography
- Adipose Tissue
- Cancer Research
- Single Dose