Pharmacology of Letro

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    Pharmacology of Letro


    The pharmacology of letrozole

    B. P. Haynes, , a, M. Dowsetta, W. R. Millerb, J. M. Dixonb and A. S. Bhatnagarc

    a Department of Academic Biochemistry, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
    b Breast Unit, Department of Clinical Oncology, Western General Hospital, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK
    c Novartis Pharma AG, CH-4002, Basel, Switzerland

    Received 10 March 2003; accepted 24 June 2003. ; Available online 18 September 2003.


    Abstract

    Recent clinical trials indicate that the third-generation aromatase inhibitors may be more effective than tamoxifen as first line endocrine therapy in ER+ metastatic breast cancer in postmenopausal women. This review will focus exclusively on the pharmacology of the non-steroidal inhibitor letrozole. Aromatase derived from a variety of sources is inhibited at low nM concentrations of the drug. In non-cellular systems, letrozole is 25 times more potent than anastrozole and exemestane in its inhibition of aromatase, whilst in cellular systems it is 1020 times more potent. Anti-tumour effects of letrozole have been demonstrated in several animal models. In postmenopausal women, letrozole commonly suppresses circulating concentrations of estrone and estradiol to below the sensitivity limit of the assays used to measure them. In a recent randomized cross-over study, letrozole (2.5 mg daily) achieved a significantly greater suppression of the plasma concentrations of both estrone and estrone sulphate than anastrozole (1 mg daily) and a greater inhibition of in vivo aromatization. Letrozole appears to have a small effect on adrenal steroidogenesis such that a small number of patients exhibit an abnormal response to synthetic ACTH during letrozole therapy. This is unlikely to have any clinical significance. In short-term studies letrozole has been shown to increase markers of bone resorption indicating the need to monitor bone integrity when the drug is used for extended periods of time. A consistent effect of letrozole on serum lipids has not been demonstrated.


    My only question to this is, What is ACTH that they are referring to in the abstract.

    db

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    ACTH is adreno-corticotrophic hormone.

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