Evaluation of CYP450 inhibitory effects and steady-state pharmacokinetics of genistein in combination with cholecalciferol and citrated zinc bisglycinate in postmenopausal women

International Journal of Women's Health

Volumn 3, Issue 1, 2011, Pages 139-150

  Burnett, Bruce P ^a   Pillai, Lakshmi ^a   Bitto, Alessandra ^b   Squadrito, Francesco ^b   Levy, Robert M ^a  

^a PRIMUS PHARMACEUTICALS INC   (United States)

^b UNIVERSITY OF MESSINA   (Italy)

Author keywords

Drug interactions; Genistein; Medical food; Metabolism; Pharmacokinetics

Indexed keywords

1 HYDROXYBUFURALOL; 4 HYDROXYTOLBUTAMIDE; 4' HYDROXYMEPHENYTOIN; 6 ALPHA HYDROXYPACLITAXEL; ALPHA HYDROXYMIDAZOLAM; BUFURALOL; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; FOSTEUM; GENISTEIN; GENISTEIN PLUS CHOLECALCIFEROL PLUS CITRATED ZINC BISGLYCINATE; HYDROXYTOLBUTAMIDE; MEPHENYTOIN; MIDAZOLAM; NUTRACEUTICAL; PACLITAXEL; PACLITAXEL DERIVATIVE; PARACETAMOL; PHENACETIN; TOLBUTAMIDE; UNCLASSIFIED DRUG;

ABSENCE OF SIDE EFFECTS; ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG UPTAKE; ENZYME INHIBITION; EVENING DOSAGE; FEMALE; FOOD; FOOD DRUG INTERACTION; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IC 50; IN VITRO STUDY; LIVER MICROSOME; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; OPEN STUDY; PLASMA CONCENTRATION-TIME CURVE; POSTMENOPAUSE; RANDOMIZED CONTROLLED TRIAL; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 79958042943     PISSN: None     EISSN: 11791411     Source Type: Journal    
DOI: 10.2147/IJWH.S19309     Document Type: Article

References (57)

1. Zhang X, Shu XO, Li H, et al. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med. 2005;165(16):1890-1895.
2. Tian Z, Wan M, Wang Z, Wang B. The preparation of genistein and LC-MS/MS on-line analysis. Drug Dev Res. 2004;61(1):6-12.
3. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006;55(1):1-12.
4. Horn-Ross PL, John EM, Lee M, et al. Phytoestrogen consumption and breast cancer risk in a multiethnic population: The Bay Area Breast Cancer Study. Am J Epidemiol. 2001;154(5):434-441.
5. De Kleijn MJ, van der Schouw YT, Wilson PW, et al. Intake of dietary phytoestrogens is low in postmenopausal women in the United States: The Framingham study(1-4). J Nutr. 2001;131(6):1826-1832.
6. Uesugi T, Fukui Y, Yamori Y. Beneficial effects of soybean isoflavone supplementation on bone metabolism and serum lipids in postmenopausal Japanese women: A four-week study. J Am Coll Nutr. 2002; 21(2):97-102.
7. Russo R, Corosu R. The clinical use of a preparation based on phytooestrogens in the treatment of menopausal disorders. Acta Biomed. 2003;74(3):137-143.
8. Casini ML, Marelli G, Papaleo E, Ferrari A, D'Ambrosio F, Unfer V. Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: A randomized, double-blind, crossover, placebo-controlled study. Fertil Steril. 2006;85(4):972-978.
9. Lund TD, Edwin D, Lephart ED. Manipulation of prenatal hormones and dietary phytoestrogens during adulthood alter the sexually dimorphic expression of visual spatial memory. BMC Neurosci. 2001;2:21.
10. Bitto A, Burnett BP, Polito F, et al. Effects of genistein aglycone in osteoporotic, ovariectomized rats: A comparison with alendronate, raloxifene and oestradiol. Br J Pharmacol. 2008;155(6):896-905.
11. Bitto A, Burnett BP, Polito F, et al. Genistein aglycone reverses glucocorticoid- induced osteoporosis and increases bone breaking strength in rats: A comparative study with alendronate. Br J Pharmacol. 2009; 156(8):1287-1295.
12. Bitto A, Polito F, Burnett B, et al. Protective effect of genistein aglycone on the development of osteonecrosis of the femoral head and secondary osteoporosis induced by methylprednisolone in rats. J Endocrinol. 2009;201(3):321-328.
13. Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: A randomized double-blind placebo-controlled study. J Bone Miner Res. 2002;17(10):1904-1912.
14. Marini H, Minutoli L, Polito F, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: A randomized trial. Ann Intern Med. 2007;146(12):839-847.
15. Marini H, Bitto A, Altavilla D, et al. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: A follow-up study. J Clin Endocrinol Metab. 2008;93(12):4787-4796.
16. Atteritano M, Mazzaferro S, Frisina A, et al. Genistein effects on quantitative ultrasound parameters and bone mineral density in osteopenic postmenopausal women. Osteoporos Int. 2009;20(11):1947-1954.
17. D'Anna R, Cannata ML, Atteritano M, et al. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: A 1-year randomized, double-blind, placebocontrolled study. Menopause. 2007;14(4):648-655.
18. Evans M, Elliott JG, Sharma P, Berman R, Guthrie N. The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: A multi-center, randomized, placebo-controlled study. Maturitas. 2011;68:189-196.
19. Sapronov NS, Kasakova SB. Effects of synthetic and plant-derived selective modulators of estrogen receptors on depression-like behavior of female rats. Bull Exp Biol Med. 2008;146(1):73-76.
20. Rodríguez-Landa JF, Hernández-Figueroa JD, Hernández-Calderón Bdel C, Saavedra M. Anxiolytic-like effect of phytoestrogen genistein in rats with long-term absence of ovarian hormones in the black and white model. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):367-372.
21. Kageyama A, Sakakibara H, Zhou W, et al. Genistein regulated serotonergic activity in the hippocampus of ovariectomized rats under forced swimming stress. Biosci Biotechnol Biochem. 2010;74(10): 2005-2010.
22. Altavilla D, Polito F, Marini H, et al. Effects of genistein aglycone on cardiovascular risk: The effects of the phytoestrogen genistein on the cardiovascular apparatus. Agrofood Industry Hi-Tech. 2008;19(5):16-17.
23. Atteritano M, Pernice F, Mazzaferro S, et al. Effects of phytoestrogen genistein on cytogenetic biomarkers in postmenopausal women: 1 year randomized, placebo-controlled study. Eur J Pharmacol. 2008; 589(1-3):22-26.
24. Taylor CK, Levy RM, Elliott JC, Burnett BP. The effect of genistein aglycone on cancer and cancer risk: A review of in vitro, preclinical, and clinical studies. Nutr Rev. 2009;67(7):398-415.
25. Coldham NG, Howells LC, Santi A, et al. Biotransformation of genistein in the rat: elucidation of metabolite structure by product ion mass fragmentology. J Steroid Biochem Mol Biol. 1999;70(4-6):169-184.
26. Heinonen SM, Hoikkala A, Wähälä K, Adlercreutz H. Metabolism of the soy isoflavones daidzein, genistein and glycitein in human subjects. Identification of new metabolites having an intact isoflavonoid skeleton. J Steroid Biochem Mol Biol. 2003;87(4-5):285-299.
27. Nieves JW. Nutritional therapies (including Fosteum). Curr Osteoporos Rep. 2009;7(1):5-11.
28. Dierks EA, Stams KR, Lim HK, Cornelius G, Zhang H, Ball SE. A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry. Drug Metab Dispos. 2001;29(1):23-29.
29. Walsky RL, Obach RS. Verification of the selectivity of (+)N-3-benzylnirvanol as a CYP2C19 inhibitor. Drug Metab Dispos. 2003;31(3):343.
30. Ayrton J, Plumb R, Leavens WJ, Mallett D, Dickins M, Dear GJ. Application of a generic fast gradient liquid chromatography tandem mass spectrometry method for the analysis of cytochrome P450 probe substrates. Rapid Commun Mass Spectrom. 1998;12(5):217-224.
31. Hersh EV, Moore PA. Drug interactions in dentistry: The importance of knowing your CYPs. J Am Dent Assoc. 2004;135(3):298-311.
32. Thomas BF, Zeisel SH, Busby MG, et al. Quantitative analysis of the principle soy isoflavones genistein, daidzein and glycitein, and their primary conjugated metabolites in human plasma and urine using reversedphase high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci Appl. 2001;760(2):191-205.
33. Holder CL, Churchwell MI, Doerge DR. Quantification of soy isoflavones, genistein and daidzein, and conjugates in rat blood using LC/ES-MS. J Agric Food Chem. 1999;47(9):3764-3770.
34. Hu M, Krausz K, Chen J, et al. Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. Drug Metab Dispos. 2003;31(7):924-931.
35. Larkin T, Price WE, Astheimer L. The key importance of soy isoflavone bioavailability to understanding health benefits. Crit Rev Food Sci Nutr. 2008;48(6):538-552.
36. Sfakianos J, Coward L, Kirk M, Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. J Nutr. 1997;127(7): 1260-1268.
37. Setchell KD, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite equol - a clue to the effectiveness of soy and its isoflavones. J Nutr. 2002;132(12):3577-3584.
38. Day AJ, DuPont MS, Ridley S, et al. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver betaglucosidase activity. FEBS Lett. 1998;436(1):71-75.
39. Ronis MJ, Little JM, Barone GW, Chen G, Radominska-Pandya A, Badger TM. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. J Med Food. 2006;9(3):348-355.
40. Prasain JK, Xu J, Kirk M, Smith Johnson M, Sfakianos J, Barnes S. Differential biliary excretion of genistein metabolites following intraduodenal and intravenous infusion of genistin in female rats. J Nutr. 2006; 136(12):2975-2979.
41. Bjornsson TD, Callaghan JT, Einolf HJ, et al. The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Dispos. 2003;31(7):815-832.
42. Craig DA. The Cheng-Prusoff relationship: Something lost in the translation. Trends Pharmacol Sci. 1993;14(3):89-91.
43. Helsby NA, Williams J, Kerr D, Gescher A, Chipman JK. The isoflavones equol and genistein do not induce xenobiotic-metabolizing enzymes in mouse and in human cells. Xenobiotica. 1997;27(6):587-596.
44. Doerge DR, Chang HC, Churchwell MI, Holder CL. Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography- mass spectrometry. Drug Metab Dispos. 2000;28(3): 298-307.
45. Roberts-Kirchhoff ES, Crowley JR, Hollenberg PF, Kim H. Metabolism of genistein by rat and human cytochrome P450s. Chem Res Toxicol. 1999;12(7):610-616.
46. Glue P, Clement RP. Cytochrome P450 enzymes and drug metabolism - basic concepts and methods of assessment. Cell Mol Neurobiol. 1999; 19(3):309-323.
47. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine. 2003;10(4):334-342.
48. Tolleson WH, Doerge DR, Churchwell MI, Marques MM, Roberts DW. Metabolism of biochanin A and formononetin by human liver microsomes in vitro. J Agric Food Chem. 2002;50(17):4783-4790.
49. Shelnutt SR, Cimino CO, Wiggins PA, Badger TM. Urinary pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein. Cancer Epidemiol Biomarkers Prev. 2000;9(4): 413-419.
50. Shelnutt SR, Cimino CO, Wiggins PA, Ronis MJ, Badger TM. Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein in men and women after consumption of a soy beverage. Am J Clin Nutr. 2002;76(3):588-594.
51. Cassidy A. Factors affecting the bioavailability of soy isoflavones in humans. J AOAC Int. 2006;89(4):1182-1188.
52. Setchell KDR, Brown NM, Desai P, et al. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr. 2001;131:1362S-1375S.
53. Bloedon LT, Jeffcoat AR, Lopaczynski W, et al. Safety and pharmacokinetics of purified soy isoflavones:Single-dose administration to postmenopausal women. Am J Clin Nutr. 2002;76(5):1126-1137.
54. Izumi T, Piskula MK, Osawa S, et al. Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. J Nutr. 2000;130(7):1695-1699.
55. Ullmann U, Oberwittle H, Grossmann M, Riegger C. Repeated oral once daily intake of increasing doses of the novel synthetic genistein product Bonistein in healthy volunteers. Planta Med. 2005;71(10):891-896.
56. Metzner JE, Frank T, Kunz I, Burger D, Riegger C. Study on the pharmacokinetics of synthetic genistein after multiple oral intake in postmenopausal women. Arzneimittelforschung. 2009;59(10):513-520.
57. Zhang Y, Song TT, Cunnick JE, Murphy PA, Hendrich S. Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations. J Nutr. 1999;129(2):399-405.