Pharmacology and Pharmacokinetics of Danazol

In: Drugs · 1980 · vol. 19(5) , pp. 321–330 · doi:10.2165/00003495-198019050-00001 · PMID:6993179 · W1996563356
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This paper reviews the pharmacology and pharmacokinetics of danazol, referencing its antiglyconeogenic activity, effects on gonadotropins, steroid blood levels, steroidogenesis, and receptor binding in various species.

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This article reviews the pharmacology and pharmacokinetics of danazol, drawing on preclinical and clinical studies in animals (e.g., rats and rhesus monkeys) and human volunteers, including work on its absorption, distribution, metabolism, receptor binding, and effects on endocrine function such as gonadotropins and steroidogenesis. Across these studies, danazol is characterized as a synthetic steroid derivative with activity consistent with inhibition of steroidogenesis and suppression of pituitary gonadotropins, with measured plasma pharmacokinetics supported by radioimmunoassays. A major caveat is that the paper is a compilation of findings from diverse referenced studies rather than a single new experiment with a unified experimental design or dosing regimen. Relevance to endometriosis: it explicitly includes an antedated symposium proceedings reference on danazol in “Recent Advances in Endometriosis,” and danazol is a historical endometriosis therapy context in the cited pharmacology summaries, though the article’s main focus is the drug’s pharmacology and pharmacokinetics.

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References Agarwal, M.K. and Coupry, F.: Antiglyconeogenic activity of gonadal steroid analogues in relation to liver glucocorticoid-receptor binding. FEBS Utters 82: 172–174 (1977). Andrews, M.C. and Wentz, A.C.: The effects of danazol on gonadotropins and steroid blood levels in normal and anovulatory women. American Journal of Obstetrics and Gynecology 121: 817–828 (1975). Asch, R.H.; Fernandez, E.O.; Smith, C.G.; Siler-Khodr, T.M. and Pauerstein, C.J.: Effects of danazol on gonadotropin levels in castrated rhesus monkeys. Obstetrics and Gynecology 53: 415–421 (1979). Barbieri, R.L.; Canick, J.A.; Makris, A.; Todd, R.B.; Davies, I.J. and Ryan, K.J.: Danazol inhibits steroidogenesis. Fertility and Sterility 28: 809–813 (1977a). Barbieri, R.L.; Canick, J.A. and Ryan, K.J.: Danazol inhibits steroidogenesis in the rats testis in vitro. Endocrinology 101: 1676–1682 (1977b). Barbieri, R.L.; Lee, H. and Ryan, K. J.: Danazol binding to rat androgen, glucocorticoid, progesterone, and estrogen receptors: Correlation with biologic activity. Fertility and Sterility 31: 182–186 (1979). Creange, J.E. and Potts, G.O.: A competitive radioligand assay for danazol using pregnant guinea pig plasma. Steroids 23: 411–420 (1974). Davison, C.; Banks, W. and Fritz, A.: The absorption, distribution and metabolic rate of Danazol in rats, monkeys, and human volunteers. Archives Internationales de Pharmacodynamie et de Therapie 221: 294–310 (1976). Dmowski, W.P.; Scholer, H.F.L.; Mahesh, V.B. and Greenblatt, R.B.: Danazol — a synthetic steroid derivative with interesting physiologic properties. Fertility and Sterility 22: 9–18 (1971). Eldridge, J.C.; Dmowski, W.P. and Mahesh, V.B.: Effects of castration of immature rats on serum FSH and LH, and of various steroid treatments after castration. Biology of Reproduction 10: 438–446 (1974). Franchimont, P. and Cramilion, C: The effect of danazol on anterior pituitary function. Fertility and Sterility 28: 814–817 (1977). Greenblatt, R.B.; Dmowski, W.P.; Mahesh, V.B. and Scholer, H.: Clinical studies with an antigonadotropin — danazol. Fertility and Sterility 22: 102–112 (1971). Hanzlik, P.J.; Lehman, A.J.; Van Winkle, W. and Kennedy, N.K.: General metabolic and glycogenic actions of propylene glycol and some other glycols. Journal of Pharmacology and Experimental Therapeutics 67: 114–126 (1939). Jones, R.C. and Edgren, R.A.: The effects of various steroids on the vaginal histology in the rat. Fertility and Sterility 24: 284–291 (1973). Kasuya, Y. and Wolff, M.E.: Uptake of androgen analogs by prostate tissue. Journal of Medicinal Chemistry 16: 832–839 (1973). Klein, M. and Parkes, A.S.: The progesterone-like action of testosterone and certain related compounds. Royal Society of London Proceeding, Series B 121: 574–579 (1937). Manson, A.J., Stonner, F.W.; Neuman, A.C.; Christiansen, R.G.; Clarke, R.L.; Ackerman, J.H.; Page, D.F.; Dean, J.W.; Phillips, D.K.; Potts, G.O.; Arnold, A.; Beyler, A.L. and Clinton, R.O.: Steroidal heterocycles. VIII. Androstano [2, 3-d] isoxazoles and related compounds. Journal of Medicinal Chemistry 6: 1–9 (1963). Pedroza, E.; Vilches-Martinez, J.A.; Arimura, A. and Schally, A. V.: Danazol effects on gonadotropin basal levels and pituitary responsiveness to LH-RH in immature male rats. Contraception 17: 61–69 (1978). Peterson, J.E.; King, M.E.; Banks, W.F.; Baker, J.F.; Jenson, A.F.; Ross, R.W. Jr.; Clemans, S. and Edelson, J.: Radioimmunoassay for danazol in human and monkey plasma. Journal of Phamaceutical Sciences 67(10): 1425–1428 (1978). Potts, G.O.: Experimental Pharmacology of Danazol, Proceedings of a Symposium on Recent Advances in Endometriosis. International Congress Series No. 368: 68–86 (1976). Potts, G.O.: Pharmacology of Danazol, Abstracts and Proceedings of a Symposium. Excerpta Medica: 47–48 (1977a). Potts, G.O.: Pharmacology of Danazol, Proceeding of a Symposium on Danol (Danazol). Journal of International Medical Research 5: 1–14 (1977b). Potts, G.O.; Beyler, A.L. and Schane, H.P.: Pituitary gonadotropin inhibitory activity of danazol. Fertility and Sterility 25: 367–372 (1974). Schane, H.P. and Potts, G.O.: Oral contraceptive activity of danazol in the rhesus monkey. Fertility and Sterility 25: 363–366 (1974). Sherins, R.J.; Gandy, H.M.; Thorslund, T.W. and Paulsen, C.A.: Pituitary and testicular function studies. I. Experience with a new gonadal inhibitor, 17α-pregn-4-en-20-yno-(2,3-d)isoxazol-17-ol (danazol). Journal of Clinical Endocrinology and Metabolism 32: 522–531 (1971). Wentz, A.C.; Jones, G.S.; Sapp, K.C. and King, T.M.: Progestational activity of danazol in the human female subject. American Journal of Obstetrics and Gynecology 126: 378–384 (1976). Williams, T.A.; Edelson, J. and Ross, R.W. Jr.: A radioimmunoassay for danazol. Steroids 3m: 206–217 (1978). Wood, G.P.; Wu, G.J.; Flickinger, G.L. and Mikhail, G.: Hormonal changes associated with danazol therapy. Obstetrics and Gynecology 45: 302–304 (1975). Author information Authors and Affiliations Rights and permissions About this article Cite this article Potts, G.O., Schane, H.P. & Edelson, J. Pharmacology and Pharmacokinetics of Danazol. Drugs 19, 321–330 (1980). https://doi.org/10.2165/00003495-198019050-00001 Published: Issue date: DOI: https://doi.org/10.2165/00003495-198019050-00001

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