Tamoxifen Aminoglutethimide

Aromatase inhibitors (including anastrozole, letrozole, aminoglutethimide, exemestane, formestane, testolactone), selective estrogen receptor modulators—SERMs (including raloxifene, tamoxifen, toremifene), clomiphene, cyclofenil, fulvestrant Diuretics, amiloride, bumetanide, canrenone, chlorthalidone, etacrynic acid, furosemide, indapamide, metolazone, spironolactone, thiazides, triamterene... 

In addition to hormonal dmgs, five other nonsteroids that have a direct relationship to this section are also nsed in cancer chemotherapy. They are aminoglutethimide, flutamide, mitotan, tamoxifen, and leuprolide. 

Carcinoma of breast (1) Adjuvant chemotherapy or tamoxifen after primary breast surgery Cyclophosphamide, doxorubicin, vincristine, methotrexate, fluorouracil, paclitaxel, mitoxantrone, prednisone, megestrol, androgens,1 aminoglutethimide, trastuzumab... 

CI0H N 769-68-6) see Aminoglutethimide Glutethimide Proxazole 2-phenylbutyrophenone (ClflH 60 16282-16-9) sec Tamoxifen 2-phenylbutyryl chloride... 

Aminoglutethimide, but not anastrozole, exemestane, or letro-zole, markedly increases tamoxifen clearance and reduces its serum levels. Tamoxifen modestly reduces anastrozole andletrozole levels, but it does not alter aminoglutethimide levels, or exemestane levels and effects. 

In 6 menopausal women with breast cancer aminoglutethimide 250 mg four times daily for 6 weeks markedly reduced the serum levels of tamoxifen 20 to 80 mg daily and most of its metabolites. The clearance of the tamoxifen was inereased by 3.2-fold and the tamoxifen AUC was re-dueed by 73% (range 56 to 80%). Conversely, the concurrent use of anastrozole 1 mg daily for 28 days did not affect the pharmacokinetics of tamoxifen in a double-blind, placebo-controlled study in 34 women with breast eaneer who had been taking tamoxifen 20 mg daily for at least 10 weeks. Similarly, letrozole 2.5 mg daily had no effeet on the pharma-eokineties of tamoxifen in 18 women taking tamoxifen 20 mg daily. Further, a study in 32 women clinically disease-free following primary treatment for breast eaneer and who had been taking tamoxifen 20 mg daily for at least 4 months found that exemestane 25 mg daily for 8 weeks... 

Tamoxifen 20 to 80 mg daily did not alter the pharmacokineties of aminoglutethimide 250 mg four times daily. In a pilot study, 18 postmenopausal women with breast cancer were gi ven exemestane 25 mg daily for 14 days, then exemestane and tamoxifen 20 mg daily for 4 weeks. Tamoxifen did not affect the pharmacokinetics (plasma levels) or pharmacodynamics (estrone, estrone sulfate and estradiol suppression) of exemestane and the eombination was well-tolerated. In 12 women letrozole levels were reduced by 38% (range 0 to 70%) 6 weeks after tamoxifen 20 mg daily was added to letrozole 2.5 mg daily. This redue-tion persisted after 4 to 8 months however, the estradiol suppressant effeets of letrozole did not appear to be affected. Similarly, although the estradiol suppressant effects of anastrozole 1 mg daily did not appear to be affeeted by tamoxifen 20 mg daily in two studies, in one of these studies, anastrozole levels were deereased by 27% by tamoxifen. ... 

It is likely that aminoglutethimide, an enzyme indueer, inereases the metabolism of the tamoxifen by the liver, thereby increasing its loss from the body. It is not known how tamoxifen reduces anastrozole and letrozole levels, although it may also be via enzyme induction. ... 

Lien EA, Anker G, Li i PE, Solheim E, Ueland PM Decreased serum cc centrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res (1990) 50, 5851-7. 

Unextracted calibrator for anti-estrogenic agents Prepared in reconstitution solvent by adding aminoglutethimide, anastrozole, letrozole metabolite (bis(cyanophenyl)methanol), clomiphene, dutasteride, exemestane, fadrozole, finasteride, formestane, fiilvestrant, 4-hydroxytamoxifen, N-desmethyltamoxifen, raloxifene, tamoxifen, testolactone, and toremifene, each at 2.5 Xg/ mL and 17a-methyltestosterone at 4.0 pg/mL. On the day of use, transfer 50 pL to a chromatographic vial and cap. 

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