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Aromatase Inhibitors pp 45–52Cite as

Clinical pharmacology of aromatase inhibitors

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References

  1. Lønning PE (2003) Clinical pharmacokinetics of aromatase inhibitors and inactivators. Clin Pharmacokinet 42: 619–631

    PubMed  Google Scholar 

  2. Yuan J, Wang PQ, Ge SR et al. (2001) Pharmacokinetics of anastrozole in Chinese male volunteers. Acta Pharmacol Sin 22: 573–576

    CAS  PubMed  Google Scholar 

  3. Pfister CU, Duval M, Godbillon J et al. (1994) Development, application and comparison of an enzyme immunoassay and a high-performance liquid chromatography method for the determination of the aromatase inhibitor CGS 20, 267 in biological fluids. J Pharm Sci 83: 520–524

    CAS  PubMed  Google Scholar 

  4. Marfil F, Pineau V, Sioufi A, Godbillon SJ (1996) High-performance liquid chromatography of the aromatase inhibitor, letrozole, and its metabolite in biological fluids with automated liquid-solid extraction and fluorescence detection. J Chromatogr B Biomed Appl 683: 251–258

    CAS  PubMed  Google Scholar 

  5. Breda M, Pianezzola E, Benedetti MS (1993) Determination of exemestane, a new aromatase inhibitor, in plasma by high-performance liquid chromatography with ultraviolet detection. J Chromatogr 620:225–231

    CAS  PubMed  Google Scholar 

  6. Sioufi A, Gauducheau N, Pineau V et al. (1997) Absolute bioavailability of letrozole in healthy postmenopausal women. Biopharm Drug Dispos 18: 779–789

    CAS  PubMed  Google Scholar 

  7. Plourde PV, Dyroff M, Dukes M (1994) Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat 30: 103–111

    Article  CAS  PubMed  Google Scholar 

  8. Cocchiara G, Allievi C, Berardi A et al. (1994) Urinary metabolism of exemestane, a new aromatase inhibitor, in rat, dog, monkey and human volunteers. J Endocrinol Invest 17: 78

    Google Scholar 

  9. Pfister C, Dowsett M, Iveson T et al. (1993) Pharmacokinetics of new aromatase inhibitor CGS 20267. Eur J Drug Metab Pharmacokinet 18(suppl.): 117

    Google Scholar 

  10. Spinelli R, Jannuzzo MG, Poggesi I et al. (1999) Pharmacokinetics (PK) of Aromasin (exemestane, EXE) after single and repeated doses in healthy postmenopausal volunteers (HPV). Eur J Cancer 35: S295

    Article  Google Scholar 

  11. Lønning PE, Bajetta E, Murray R et al. (2000) Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol 18: 2234–2244

    PubMed  Google Scholar 

  12. Longcope C (1972) The metabolism of estrone sulfate in normal males. J Clin Endocrinol Metab 34: 113–122

    CAS  PubMed  Google Scholar 

  13. Murray M, Cantrill E, Farrell GC (1993) Induction of cytochrome P450 2B1 in rat liver by the aromatase inhibitor aminoglutethimide. J Pharmacol Exp Ther 265: 477–481

    CAS  PubMed  Google Scholar 

  14. Lien EA, Anker G, Lønning PE et al. (1990) Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res 50: 5851–5857

    CAS  PubMed  Google Scholar 

  15. Lundgren S, Lonning PE, Aakvaag A (1990) Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer. Cancer Chemother Pharmacol 27: 101–105

    Article  CAS  PubMed  Google Scholar 

  16. Van Deijk WA, Blijham GH, Mellink WA, Meulenberg PM (1985) Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate: its correlation with serum cortisol. Cancer Treat Rep 69: 85–90

    PubMed  Google Scholar 

  17. Haynes BP, Dowsett M, Miller WR et al. (2003) The pharmacology of letrozole. J Steroid Biochem Mol Biol 87: 35–45

    Article  CAS  PubMed  Google Scholar 

  18. Dowsett M, Tobias JS, Howell A et al. (1999) The effect of anastrozole on the pharmacokinetics of tamoxifen in post-menopausal women with early breast cancer. Br J Cancer 79: 311–315

    CAS  PubMed  Google Scholar 

  19. Dowsett M, Cuzick J, Howell A, Jackson I (2001) Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the’ Arimidex and tamoxifen alone or in combination ‘(ATAC) trial. Br J Cancer 85: 317–324

    CAS  PubMed  Google Scholar 

  20. Purba HS, Bhatnagar A (1990) A comparison of methods measuring aromatase activity in human placenta and rat ovary. J Enzyme Inhib 4: 169–178

    CAS  PubMed  Google Scholar 

  21. Brodie A, Lu Q, Liu Y, Long B (1999) Aromatase inhibitors and their antitumor effects in model systems. Endocr Relat Cancer 6: 205–210

    Article  CAS  PubMed  Google Scholar 

  22. Miller WR, Dixon JM (2000) Antiaromatase agents: preclinical data and neoadjuvant therapy. Clin Breast Cancer (suppl.): S9–S14

    Google Scholar 

  23. Geisler J, Lønning PE (2005) Aromatase inhibition — translation into a succesful therapeutic approach. Clin Cancer Res 11(8): 2809–2821

    CAS  PubMed  Google Scholar 

  24. Thompson EA Jr, Siiteri PK (1974) The involvement of human placental microsomal cytochrome P-450 in aromatization. J Biol Chem 249: 5373–5378

    CAS  PubMed  Google Scholar 

  25. Steele RE, Mellor LB, Sawyer WK et al. (1987) In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS 16949A. Steroids 50: 147–161

    Article  CAS  PubMed  Google Scholar 

  26. Bossche HV, Willemsens G, Roels I et al. (1990) R 76713 and enantiomers: selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis. Biochem Pharmacol 40:1707–1718

    Article  Google Scholar 

  27. Dukes M, Edwards PN, Large M et al. (1996) The preclinical pharmacology of “Arimidex” (anastrozole; ZD1033) — a potent, selective aromatase inhibitor. J Steroid Biochem Mol Biol58:439–445

    Article  CAS  PubMed  Google Scholar 

  28. Bhatnagar AS, Hausler A, Schieweck K et al. (1990) Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor. J Steroid Biochem Mol Biol 37: 1021–1027

    CAS  PubMed  Google Scholar 

  29. Brodie AM, Wing LY (1987) In vitro and in vivo studies with aromatase inhibitor 4-hydroxyandrostenedione. Steroids 50: 89–103

    Article  CAS  PubMed  Google Scholar 

  30. Di Salle E, Briatico G, Giudici D et al. (1994) Novel aromatase and 5 alpha-reductase inhibitors. J Steroid Biochem Mol Biol 49: 289–294

    PubMed  Google Scholar 

  31. Batzl C, Hausler A, Schieweck K et al. (1996) Pharmacology of nonsteroidal aromatase inhibitors. In: Pasqualini J, Katzenellenbogen B (eds): Hormone-dependent cancer. Marcel Dekker, New York, 155–168

    Google Scholar 

  32. Batzl-Hartmann C, Evans DB, Bhatnagar A (2003) Comparative aromatase enzyme kinetic studies on fadrozole, formestane, letrozole, anastrozole and exemestane. 26th San Antonio Breast Cancer Symposium, San Antonio, TX, USA. Date: December 3–6, 2003. Proceedings published in: Breast Cancer Research and Treatment, Vol. 82, Supplement 1, Abstract 458, page S111, 2003. Kluver Academic Publishers

    Google Scholar 

  33. Lønning PE, Jacobs S, Jones A et al. (1991) The influence of CGS 16949A on peripheral aromatization in breast cancer patients. Br J Cancer 63: 789–793

    PubMed  Google Scholar 

  34. Geisler J, Haynes B, Anker G et al. (2002) Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 20:751–757

    Article  CAS  PubMed  Google Scholar 

  35. Kochak GM, Mangat S, Mulagha MT et al. (1990) The harmacodynamic inhibition of estrogen synthesis by fadrozole, an aromatase inhibitor, and its pharmacokinetic disposition. J Clin Endocrinol Metab 71: 1349–1355

    CAS  PubMed  Google Scholar 

  36. Santen RJ, Santner S, Davis B et al. (1978) Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 47:1257–1265

    CAS  PubMed  Google Scholar 

  37. Lønning PE, Geisler J, Johannessen DC, Ekse D (1997) Plasma estrogen suppression with aromatase inhibitors evaluated by a novel, sensitive assay for estrone sulphate. J Steroid Biochem Mol Biol 61: 255–260

    PubMed  Google Scholar 

  38. Jacobs S, Lønning PE, Haynes B et al. (1991) Measurement of aromatisation by a urine technique suitable for the evaluation of aromatase inhibitors in vivo. J Enzyme Inhib 4: 315–325

    CAS  PubMed  Google Scholar 

  39. Dowsett M, Jones A, Johnston SR et al. (1995) In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Cancer Res 1:1511–1515

    CAS  PubMed  Google Scholar 

  40. MacNeill FA, Jones AL, Jacobs S et al. (1992) The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. Br J Cancer 66: 692–697

    CAS  PubMed  Google Scholar 

  41. MacNeill FA, Jacobs S, Dowsett M et al. (1995) The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients. Cancer Chemother Pharmacol 36: 249–254

    CAS  PubMed  Google Scholar 

  42. Jones AL, MacNeill F, Jacobs S et al. (1992) The influence of intramuscular 4-hydroxyandrostenedione on peripheral aromatisation in breast cancer patients. Eur J Cancer 28A:1712–1716

    CAS  PubMed  Google Scholar 

  43. Geisler J, King N, Dowsett M et al. (1996) Influence of anastrozole (Arimidex), a selective, nonsteroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer. Br J Cancer 74: 1286–1291

    CAS  PubMed  Google Scholar 

  44. Geisler J, King N, Anker G et al. (1998) In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 4:2089–2093

    CAS  PubMed  Google Scholar 

  45. Thürlimann B, Castiglione M, HsuSchmitz SF et al. (1997) Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer 33:1017–1024

    Article  PubMed  Google Scholar 

  46. Buzdar AU, Smith R, Vogel C et al. (1996) Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma. Results of two randomized double blind controlled multiinstitutional trials. Cancer 77: 2503–2513

    Article  CAS  PubMed  Google Scholar 

  47. Falkson CI, Falkson HC (1996) A randomised study of CGS 16949A (fadrozole) versus tamoxifen in previously untreated postmenopausal patients with metastatic breast cancer. Ann Oncol 7:465–469

    CAS  PubMed  Google Scholar 

  48. Thürlimann B, Beretta K, Bacchi M et al. (1996) First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer — Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88. Ann Oncol 7: 471–479

    PubMed  Google Scholar 

  49. Pérez-Carrión R, Candel VA, Calabresi F et al. (1994) Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Ann Oncol 5:S19–S24

    PubMed  Google Scholar 

  50. Geisler J, Berntsen H, Lønning PE (2000) A novel HPLC-RIA method for the simultaneous detection of estrone, estradiol and estrone sulphate levels in breast cancer tissue. J Steroid Biochem Mol Biol 72: 259–264

    Article  CAS  PubMed  Google Scholar 

  51. Geisler J (2003) Breast cancer tissue estrogens and their manipulation with aromatase inhibitors and inactivators. J Steroid Biochem Mol Biol 86: 245–253

    Article  CAS  PubMed  Google Scholar 

  52. Van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH (1985) Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res 45:2900–2906

    PubMed  Google Scholar 

  53. Pasqualini JR, Cortes-Prieto J, Chetrite G et al. (1997) Concentrations of estrone, estradiol and their sulfates, and evaluation of sulfatase and aromatase activities in patients with breast fibroadenoma. Int J Cancer 70:639–643

    Article  CAS  PubMed  Google Scholar 

  54. Geisler J, Detre S, Berntsen H et al. (2001) Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer. Clin Cancer Res 7:1230–1236

    CAS  PubMed  Google Scholar 

  55. Sluijmer AV, Heineman MJ, De Jong FH, Evers JL (1995) Endocrine activity of the postmenopausal ovary: the effects of pituitary down-regulation and oophorectomy. J Clin Endocrinol Metab 80: 2163–2167

    Article  CAS  PubMed  Google Scholar 

  56. Bolt HM (1979) Metabolism of estrogens-natural and synthetic. Pharmacol Ther 4: 155–181

    Article  CAS  PubMed  Google Scholar 

  57. Miller WR, Mullen P, Sourdaine P (1997) Regulation of aromatase activity within the breast. J Steroid Biochem Mol Biol 61: 193–202

    Article  PubMed  Google Scholar 

  58. de Jong PC, Blankenstein MA, van de Ven J et al. (2001) Importance of local aromatase activity in hormone-dependent breast cancer: a review. Breast 10: 91–99

    PubMed  Google Scholar 

  59. Bulun SE, Takayama K, Suzuki T et al. (2004) Organization of the human aromatase p450 (CYP19) gene. Semin Reprod Med 22: 5–9

    CAS  PubMed  Google Scholar 

  60. Reed MJ, Aherne GW, Ghilchik MW et al. (1991) Concentrations of oestrone and 4-hydroxyandrostenedione in malignant and normal breast tissues. Int J Cancer 49: 562–565

    CAS  PubMed  Google Scholar 

  61. de Jong PC, van de Ven J, Nortier HW et al. (1997) Inhibition of breast cancer tissue aromatase activity and estrogen concentrations by the third-generation aromatase inhibitor vorozole. Cancer Res 57: 2109–2111

    PubMed  Google Scholar 

  62. Miller WR, Telford J, Love CD et al. (1998) Effects of letrozole as primary medical therapy on in situ oestrogen synthesis and endogenous oestrogen levels within the breast. Breast 7: 273–276

    Article  Google Scholar 

  63. Johannessen DC, Engan T, Di Salle E et al. (1997) Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study. Clin Cancer Res 3: 1101–1108

    CAS  PubMed  Google Scholar 

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  1. Department of Medicine, Section of Oncology, Haukeland University Hospital, 5021, Bergen, Norway

    Jürgen Geisler & Per Eystein Lønning

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  1. Jürgen Geisler
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  1. AstraZeneca, Global Discovery, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK

    Barrington J.A. Furr

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Geisler, J., Lønning, P.E. (2006). Clinical pharmacology of aromatase inhibitors. In: Furr, B.J. (eds) Aromatase Inhibitors. Milestones in Drug Therapy MDT. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7418-7_3

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