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Xenobiotica
the fate of foreign compounds in biological systems
Volume 48, 2018 - Issue 10
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General Xenobiochemistry

Metabolism of megestrol acetate in vitro and the role of oxidative metabolites

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Pages 973-983 | Received 14 Aug 2017, Accepted 26 Sep 2017, Published online: 10 Nov 2017

References

  • Aguilar DC, Strom J, Xu B, et al. (2013). Expression of glucocorticoid-induced leucine zipper (GILZ) in cardiomyocytes. Cardiovasc Toxicol 13:91–9
  • Argiles JM, Anguera A, Stemmler B. (2013). A new look at an old drug for the treatment of cancer cachexia: megestrol acetate. Clin Nutr 32:319–24
  • Benitez A, Yates TJ, Shamaldevi N, et al. (2013). Dietary supplement hymecromone and sorafenib: a novel combination for the control of renal cell carcinoma. Investig Urol 190:285–90
  • Bentel JM, Birrell SN, Pickering MA, et al. (1999). Androgen receptor agonist activity of the synthetic progestin, medroxyprogesterone acetate, in human breast cancer cells. Mol Cell Endocrinol 154:11–20
  • Bristol-Myers Squibb Canada. (2014). Megace* OS (megestrol acetate) Oral suspension USP, 40 mg/ml [Product monograph] Montreal, Canada, H4S 0A4
  • Cooper JM, Kellie AE. (1968). The metabolism of megestrol acetate (17-alpha-acetoxy-6-methylpregna-4,6-diene-3,20-dione) in women. Steroids 11:133–49
  • Desta Z, Ward BA, Soukhova NV, Flockhart D. (2004). Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 310:1062–72
  • Emoto C, Iwasaki K. (2006). Enzymatic characteristics of CYP3A5 and CYP3A4: a comparison of in vitro kinetic and drug-drug interaction patterns. Xenobiotica 36:219–33
  • Gasser R, Funk C, Matzinger P, et al. (1999). Use of transgenic cell lines in mechanistic studies of drug metabolism. Toxicol In Vitro 13:625–32
  • Ghatge RP, Jacobsen MB, Schittone SA, Horowitz KB. (2005). The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells. Breast Can Res 7:R1036–R1050
  • Govender Y, Avenant C, Verhoog NJD, et al. (2014). The injectable-only contraceptive medroxyprogesterone acetate, unlike northisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor. PLoS One 9:e96497
  • Graham KK, Mikolich DJ, Fisher AE, et al. (1994). Pharmacologic evaluation of megestrol acetate oral suspension in cachectic AIDS patients. J Acquir Immune Defic Syndr 7:580–6
  • Houston JB, Galetin A. (2005). Modelling atypical CYP3A4 kinetics: principles and pragmatism. Arch Biochem Biophys 433:351–60
  • Huang Z, Roy P, Waxman DJ. (2000). Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzing N-dechloroethylation of cyclophosphamide and ifosfamide. Biochem Pharmacol 59:961–72
  • Hustert E, Haberl M, Burk O, et al. (2001). The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 11:1773–9
  • Kobayashi K, Mimura N, Fujii H, et al. (2000). Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate. Clin Cancer Res 6:3297–303
  • Korzekwa KR, Krishnamachary N, Shou M, et al. (1998). Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry 37:4137–47
  • Koubovec D, Ronacher K, Stubsrud E, et al. (2005). Synthetic progestins used in HRT have different glucocorticoid agonist properties. Mol Cell Oncol 242:23–32
  • Lohitnavy M, Methaneethorn J, Chiang-Ngernthanyakool R, et al. (2015). Pharmacokinetic model for the inhibition of simvastatin metabolism by itraconazole. Conc Proc IEEE Eng Biol Soc 2015:3246–9
  • Mantovani G, Maccio A, Lai P, et al. (1998). Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 9:99–106
  • Matin K, Egorin MJ, Ballesteros MF, et al. (2002). Phase I and pharmacokinetic study of vinblastine and high-dose megestrol acetate. Cancer Chemother Pharmacol 50:179–85
  • McCarthy HD, Crowder RE, Dryden S, Williams G. (1994). Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations. Eur J Pharmacol 265:99–102
  • Mikosz CA, Brickley DR, Sharkey MS, et al. (2001). Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, SGK-1*. J Biol Chem 276:16649–54
  • Musgrove EA, Lee CS, Sutherland RL. (1991). Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor alpha, epidermal growth factor receptor, c-fos, and c-myc genes. Mol Cell Biol 11:5032–43
  • Nishino T, Ishibashi K, Hirtreiter C, Nishino Y. (2009). Potentiation of the antitumor effect of tamoxifen by combination with the antiprogestin onapristone. J Steroid Biochem Mol Biol 116:187–90
  • Pu YS, Cheng AL, Chen J, et al. (1998). Megestrol acetate antagonizes cisplatin cytotoxicity. Anticancer Drugs 9:733–8
  • Ramírez J, Liu W, Mirkov S, et al. (2007). Lack of association between common polymorphisms in UGT1A9 and gene expression and activity. Drug Metab Dispos 35:2149–53
  • Schacter L, Rozencweig M, Canetta R, et al. (1989). Megestrol acetate: clinical experience. Cancer Treat Rev 16:49–63
  • Skor M, Wonder E, Kocherginsky M, et al. (2013). Glucocorticoid receptor antagonism as a novel therapy for triple-negative breast cancer. Clin Can Res 19:6163–72
  • Tisdale MJ. (1997). Biology of cachexia. J Natl Cancer Inst 23:1763–73
  • Turgeon D, Carrier J-S, Chouinard S, Belanger A. (2003). Glucuronidation activity of the UGT2B17 enzyme toward xenobiotics. Drug Metab Dispos 31:670–6
  • Varhe A, Olkkola KT, Neuvonen PJ. (1996). Diltiazem enhances the effects of triazolam by inhibiting its metabolism. Clin Phamacol Ther 59:369–75
  • Warren MP. (2008). Is megestrol acetate a suitable option for treatment of hot flashes in women with breast cancer? Nat Clin Pract Endocrinol Metab 4:650–1
  • Yeh SS, Schuster MW. (2006). Megestrol acetate in cachexia and anorexia. Int J Nanomedicine 1:411–16
  • Yin P, Roqueiro D, Huand L, et al. (2012). Genome-wide progesterone receptor binding: cell type specific and shared mechanisms in T47D breast cancer cells and primary leiomyoma cells. PLoS One 7:e29021
  • Zhou-Pan XR, Seree E, Zhou XJ, et al. (1993). Involvement of human liver cytochrome P450 3A in vinblastine metabolism: drug interactions. Cancer Res 53:5121–6
  • Zhou X, Zheng N, Felix CA, Blair IA. (2004). Kinetics and regulations of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos 32:993–1000

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