Exemestane

Molecular formula C20H24O2 Molecular weight 296.40 CAS Registry No 107868-30-4 Merck Index 13, 3944 

Sample preparation Mix 1 mL plasma with 100 aL 1 (xg/mL IS in water, add 600 ixL 500 mM pH 7.4 potassium phosphate buffer, mix, add 3 mL dichloromethaneiisooctane 40 60, shake for 10 min, centrifuge at 1200 g for 15 min, repeat the extraction. Combine the organic layers and evaporate them to dryness vmder a stream of nitrogen at 37, reconstitute the residue with 200 p.L MeCNiwater 50 50, inject a 150 iL aUquot. 

Guard column 37-53 xm pellicular ODS Column 125 x 4.6 5 jxm Lichrocart RP18 

Mobile phase MeCN 50 mM pH 4.5 potassium phosphate buffer 35 65 Flow rate 1.5 Injection volume 150 Detector UV 247 

Hanezzola, E. Strolin Benedetti, M.S. Determination of exemestane, a new aromatase inhibitor, in plasma by high-performance hquid chromatography with ultraviolet detection, J.Chroma-togr., 1993, 620, 225 231. 

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Equilibrium expression, 19 Equimolar potency ratios, 200-201 Etodolac, 154f Evaporation rate, 10, 12 Exemestane, 163f Experiment(s)... 

Chronic renal disease Aromatase inhibitors (anastrazole, exemestane, letrozole)... 

Exemestane is an irreversible aromatase inactivator that binds to the aromatase enzyme to block the production of estrogen from androgens. Exemestane is absorbed rapidly after oral administration, with a terminal half-life of 24 hours. The drug is eliminated primarily by the liver and feces, with less than 1% of the dose excreted unchanged in the urine. Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women who have had disease progression following tamoxifen therapy. Side effects include hot flashes, fatigue, osteoporosis/bone fractures, and flulike symptoms. 

Successful coadministration of bisphosphonates with the aro-matase inhibitors has been accomplished in many patients in the metastatic setting. The three available aromatase inhibitors are exemestane, anastrozole, and letrozole. 

Nonsteroidal Steroidal Anastrozole Letrozole Exemestane 1 mg orally daily 2.5 mg orally daily 25 mg orally daily Hot flashes, arthralgias, myalgias, headaches, diarrhea, mild nausea, osteoporosis (boneloss)... 

Options for adjuvant hormonal therapy in postmenopausal women include aromatase inhibitors (e.g. anastrozole, letrozole, or exemestane) either in place of or after tamoxifen. Adverse effects with aromatase inhibitors include hot flashes, myalgia/arthralgia, vaginal dryness/atrophy, mild headaches, and diarrhea. 

Steroidal Exemestane 25 mg orally daily diarrhea, mild nausea... 

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... 

Currently, anastrozole and letrozole are efficacious in early-stage, locally advanced, and mefasfafic disease and fhus they present with the most complete data set for the different stages of breast cancer. Although it seems rather unlikely that one will be able to detect differences with respect to clinical effects at the tumour level, the indirect comparison of different AIs suggests a stronger evidence for the use of exemestane compared with other AIs for breast cancer therapy [90]. 

Anastrozole (Arimidex) Bicalutamide (Casodex) Estramustine Phosphate (Estracyt, Emcyt) Exemestane (Aromasin) Fluoxymesterone (Halotestin, Androxy)... 

AROMATASE INHIBITORS FOR BREAST CANCER EXEMESTANE (AROMASIN ), ANASTROZOLE (ARIMIDEX ), AND LETROZOLE (FEMARA )... 

Despite the significant benefit that tamoxifen has bestowed on breast cancer patients, the third-generation aromatase inhibitors are rapidly replacing tamoxifen as the first-Une treatment for breast cancers. In this chapter, focus will be given to three representative small-molecule aromatase inhibitors for breast cancer exemestane (1, Aromasin ), anastrozole (2, Arimidex ), and letrozole (3, Femara ). 

Aromatase inhibitors may be classified into two types. Type 1 aromatase inhibitors bind to the aromatase enzyme irreversibly, so they are called inactivators. In some cases they are dubbed mechanism-based or suicide inhibitors when they are metabolized by the enzyme into reactive intermediates that bind covalently to the active site. Type 1 aromatase inhibitors are usually steroidal in structure as represented by exemestane (1), formestane (13), and atamestane (14). Formestane (13) was launched by Ciba-Geigy in 1992. As formestane (13) is readily and extensively metabohzed when administered orally, it is used as a depot formulation for injection. 

SYNTHESIS OF EXEMESTANE (Buzzetti, 1989 Di Salle and Zaccheo, 1992 Longo and Lambardi, 1989)... 

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