Pharmacokinetic evaluation of bazedoxifene for the treatment of osteoporosis

Expert Opinion on Drug Metabolism and Toxicology

Volumn 9, Issue 7, 2013, Pages 883-892

  Gatti, Davide ^a   Rossini, Maurizio ^a   Sblendorio, Ignazio ^b   Lello, Stefano ^c  

^a UNIVERSITY OF VERONA   (Italy)

^b SRL   (Italy)

^c LABORATORIO DI PATOLOGIA VASCOLARE   (Italy)

Author keywords

Bazedoxifene; Menopause; Osteoporosis; SERM

Indexed keywords

BAZEDOXIFENE; CONJUGATED ESTROGEN; DIAZEPAM; DIGOXIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; RALOXIFENE; TAMOXIFEN; WARFARIN;

ARTICLE; BINDING AFFINITY; BONE DENSITY; BONE MASS; BONE REMODELING; BONE TURNOVER; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENDOMETRIAL THICKNESS; HIGH RISK PATIENT; HOT FLUSH; HUMAN; INCIDENCE; LEG CRAMP; LIPID METABOLISM; MENOPAUSAL SYNDROME; NONHUMAN; OSTEOLYSIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POST HOC ANALYSIS; POSTMENOPAUSE OSTEOPOROSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REPRODUCTION; SPINE FRACTURE; TRABECULAR BONE; VENOUS THROMBOEMBOLISM;

AGED; DRUG EVALUATION; ESTROGENS, CONJUGATED (USP); FEMALE; HUMANS; INDOLES; MENOPAUSE; OSTEOPOROSIS, POSTMENOPAUSAL; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SPINAL FRACTURES; TREATMENT OUTCOME;

EID: 84879232797     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2013.794221     Document Type: Article

References (58)

1. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-33 (Pubitemid 44607392)
2. Kanis JA, Johnell O. Requirements for DXA for the management of osteoporosis in Europe. Osteoporos Int 2005;16(3):229-38 (Pubitemid 40379422)
3. Gambacciani M, Vacca F. Postmenopausal osteoporosis and hormone replacement therapy. Minerva Med 2004;95:507-20
4. National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis. 2010. Available from: http://www.nof. org/sites/default/files/pdfs/NOF-ClinicianGuide2009-v7.pdf
5. MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 2008;148:197-213 (Pubitemid 351665507)
6. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33 (Pubitemid 34761611)
7. Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291(14):1701-12
8. Hendrix SL, Wassertheil-Smoller S, Johnson KC, et al. Effects of conjugated equine estrogen on stroke in the Women's Health Initiative. Circulation 2006;113:2425-34 (Pubitemid 43948050)
9. Lindsay R. Preventing osteoporosis with a tissue selective estrogen complex (TSEC) containing bazedoxifene/conjugated estrogens (BZA/CE). Osteoporos Int 2011;22:447-51
10. National Osteoporosis Guideline Group Osteoporosis. Clinical guideline for prevention and treatment. Executive Summary. Updated July 2010
11. Reginster JY. Antifracture efficacy of currently available therapies for postmenopausal osteoporosis. Drugs 2011;71(1):65-78
12. Shelly W, Draper MW, Krishnan V, et al. Selective estrogen receptor modulators: an update on recent clinical findings. Obstet Gynecol Survey 2008;63(3):163-81. (Pubitemid 351612435)
13. Komm BS, Lyttle CR. Developing a SERM: stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann NY Acad Sci 2001;949:317-26 (Pubitemid 34059996)
14. Arun B, Anthony M, Dunn B. The search for the ideal SERM. Expert Opin Pharmacother 2002;3:681-91 (Pubitemid 34649697)
15. Palacios S. Third generation SERMs: anything new? Maturitas 2010;67(2):101-2
16. Komm BS, Kharode YP, Bodine PV, et al. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology 2005;146(9):3999-4008. (Pubitemid 41175771)
17. Gruber C, Gruber D. Bazedoxifene. Curr Opin Investig Drugs 2004;5:1086-93
18. Chandrasekaran A, Ermer J, McKeand W, et al. Bazedoxifene acetate metabolic disposition in healthy postmenopausal women. J Clin Pharmacol Ther 2003;73:47
19. Chandrasekaran A, McKeand WE, Sullivan P, et al. Metabolic disposition of [14C] bazedoxifene in healthy, postmenopausal women. Drug Metab Dispos 2009;37(6):1219-25
20. European Medicines Agency. Assessment report for Conbriza [online]. Available from: http://www.ema.europa.eu/docs/en-GB/document-library/EPAR- Public-assessment-report/human/000913/WC500033576.pdf
21. Miller CP, Collini MD, Tran BD, et al. Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. J Med Chem 2001;44:1654-7 (Pubitemid 32852172)
22. Ronkin S, Northington R, Baracat E, et al. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol 2005;105:1397-404. (Pubitemid 40734275)
23. Boudes P, Ronkin S, Korner P, et al. Effects of bazedoxifene TSE-424, a novel tissue selective estrogen receptor modulator SERM, on the incidence of breast pain. Osteoporos Int 2003;14(Suppl 7):S14.
24. Ronkin S, Baracat E, Roma L, et al. TSE-424, a novel tissue selective estrogen, reduces biochemical indices of bone metabolism in a dose related fashion. Endocrine Society program and abstracts of the 83rd Annual Meeting; 20-23 June 2001; Denver, CO, USA.
25. Miller PD, Chines AA, Christiansen C, et al. Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res 2008;23(4):525-35 . Key trial showing that the bazedoxifene prevents postmenopausal bone loss and reduces bone turnover markers equally as well as raloxifene. (Pubitemid 351501893)
26. Silverman SL, Christiansen C, Genant HK, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res 2008;23(12):1923-34 . Key registrative trial establishing the antifracture efficacy of bazedoxifene.
27. Pinkerton JV, Archer DF, Utian WH, et al. Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis. Menopause 2009;16(6):1102-8 .
28. Kanis JA, Johansson H, Oden A, McCloskey EV. Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX. Bone 2009;44:1049-54.
29. Kanis JA, Oden A, Johansson H, et al. FRAX and its applications to clinical practice. Bone 2009;44:734-43
30. Silverman SL, Chines AA, Kendler DL, et al. Bazedoxifene Study Group. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study. Osteoporos Int 2012;23(1):351-63.
31. Palacios S, Silverman S, Levine AB, et al. Long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled study. Climacteric 2011;14(Suppl 1):59-60 Abs of oral presentation at 13th World Congress on the Menopause, Rome, Italy, 8-11 June 2011 . 7 year extension of the original 3-year trial that confirmed antifracture efficacy of bazedoxifene after 7 years of treatment.
32. Archer DF, Pinkerton JV, Utian WH, et al. Bazedoxifene, a selective estrogen receptor modulator: effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women. Menopause 2009;16(6):1109-15
33. Harvey JA, Holm MK, Ranganath R, et al. The effects of bazedoxifene on mammographic breast density in postmenopausal women with osteoporosis. Menopause 2009;16:1193-6
34. Bachman G, Crosby U, Feldman RA, et al. Effects of bazedoxifene in nonflushing postmenopausal women: a randomized phase 2 trial. Menopause 2011;18(5):508-14
35. de Villiers TJ, Kendler D, Chines A, et al. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int 2011;22:567-76
36. Crabtree JS, Peano BJ, Zhang X, et al. Activity of three selective estrogen receptor modulators on ormonedependent responses in the mouse uterus and mammary gland. Mol Cell Endocrinol 2008;287(1-2):40-6
37. Kharode Y, Bodine PV, Miller CP, et al. The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. Endocrinology 2008;149(12):6084-91
38. Stefanick ML, Anderson GL, Margolis KL, et al. for the WHI Investigators. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006;295:1647-57
39. Lindsay R, Gallagher JC, Kagan R, et al. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril 2009;92:1045-52
40. Pickar JH, Yeh IT, Bachmann G, Speroff L. Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conjugated estrogens as a menopausal therapy. Fertil Steril 2009;92:1018-24
41. Harvey JA, Pinkerton JV, Baracat EC, et al. Evaluation of changes in mammographic breast density associated with bazedoxifene/conjugated estrogens in postmenopausal women. Endocr Rev 2011;32(3):P1-P79
42. Pinkerton JA, Constantine GD, Komm BS, et al. Breast effects of bazedoxifene/conjugated estrogens in a randomized, controlled trial of postmenopausal women [abstract P-46]. Poster presented at: the 19th Annual Meeting of the North American Menopause Society; 24-27 September 2008; Lake Buena Vista, FL, USA; 2008
43. Pinkerton JV, Taylor H, Pan K, et al. Breast parameters with bazedoxifene/conjugated estrogens in randomized, controlled trials of postmenopausal women. Menopause 2010;17(6):1221-2
44. Pinkerton JV, Utian WH, Constantine GD, et al. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: a randomized, controlled trial. Menopause 2009;16(6):1116-24
45. Lobo RA, Pinkerton JV, Gass ML, et al. Evaluation of bazedoxifene/ conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril 2009;92(3):1025-38
46. Kagan R, Williams RS, Pan K, et al. A randomized, placebo-and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women. Menopause 2010;17(2):281-9
47. Wells GA, Cranney A, Peterson J, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008(1):CD001155
48. Wells G, Cranney A, Peterson J, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008(1):CD004523
49. Chesnut CHI, Skag A, Christiansen C, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 2004;19:1241-9 (Pubitemid 41094364)
50. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809-22 (Pubitemid 46698462)
51. Hochberg MC. Nonvertebral fracture risk reduction with nitrogen-containing bisphosphonates. Curr Osteoporos Rep 2008;6:89-94
52. Harris ST, Blumentals WA, Miller PD. Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies. Curr Med Res Opin 2008;24:237-45 (Pubitemid 351160255)
53. Rossini M, Bianchi G, Di Munno O, et al. Treatment of Osteoporosis in clinical Practice (TOP) Study Group. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 2006;17(6):914-21 (Pubitemid 43781506)
54. Rossini M, Di Munno O, Gatti D, et al. Optimising bisphosphonate treatment outcomes in postmenopausal osteoporosis: review and Italian experience. Clin Exp Rheumatol 2011;29(4):728-35
55. Papapetrou PD. Bisphosphonate-associated adverse events. Hormones 2009;8(2):96-110
56. Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc 2009;84(7):632-8
57. Ruggiero SL, Mehrotra B. Bisphosphonate-related osteonecrosis of the jaw: diagnosis, prevention, and management. Annu Rev Med 2009;60:85-96
58. Peano BJ, Crabtree JS, Komm BS, et al. Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland. Endocrinology 2009;150(4):1897-903