Nonsteroidal aromatase inhibitor

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

Like anastrozole, letrozole is a third generation, type II nonsteroidal aromatase inhibitor. Renal excretion of its... 

Cavalli A, Greco G, Novellino E, Recanatini M. Linking CoMFA and protein homology models of enzyme-inhibitor interactions an application to nonsteroidal aromatase inhibitors. Bioorg Med Chem 2000 8 2771-80. 

Anastrozole is a selective nonsteroidal aromatase inhibitor that lowers estrogen levels. The pharmacokinetics of anastrozole demonstrate good absorption, with hepatic metabolism the primary route of elimination and only 10% excreted unchanged by the kidney. The elimination half-life is approximately 50 hours. Anastrozole is used for the adjuvant treatment of postmenopausal women with hormone-positive breast cancer and in breast cancer patients who have had disease progression following tamoxifen. Side effects include hot flashes, arthralgias, osteoporosis/bone fractures, and thrombophlebitis. 

Anastrazole -nonsteroidal aromatase inhibitor -nausea and vomiting -bowel changes (diarrhea or constipation) -headache -peripheral edema -hot flashes... 

Shozu M, Murakami K, Segawa T, Kasai T, Inoue M (2003) Successful treatment of a symptomatic uterine leiomyoma in a perimenopausal woman with a nonsteroidal aromatase inhibitor. Fertil Steril 79 628-631... 

Anastrozole (Arimidex) [Antineoplastic/Nonsteroidal Aromatase Inhibitor] Uses Breast CA postmenopausal w/ met breast CA, adjuvant Rx postmenopausal early hormone-rec tor(+) breast CA Action Selective nonsteroidal aromatase inhibitor, X circ estradiol Dose 1 mg/d Caution [D, ] Contra PRO Disp Tabs SE D, HTN, flushing, t bone/tumor pain, HA, somnolence Interactions None noted EMS May cause vag bleeding during 1st few wks of Tx OD May cause NA, abd discomfort, and bloody stools symptomatic and supportive... 

Finrozole is a nonsteroidal competitive aromatase inhibitor that is being evaluated in Phase II trials for the treatment of lower urinary tract symptoms associated with a reduced androgen/estrogen ratio in aging males associated with BPH. 

Several other aromatase inhibitors are undergoing clinical trials in patients with breast cancer. Fadrozole is an oral nonsteroidal (triazole) inhibitor of aromatase activity. These compounds appear to be as effective as tamoxifen. In addition to their use in breast cancer, aromatase inhibitors have been successfully employed as adjuncts to androgen antagonists in the treatment of precocious puberty and as primary treatment in the excessive aromatase syndrome. 

Uses Advanced breast CA in postmenopausal Action Nonsteroidal aromatase inhibitor Dose 2.5 mg/d PO Caution [D, ] Contra PRG Disp Tabs SE Anemia, N, hot flashes, arthralgia Interactions T Risk of interference w/ action of drug W/ estrogens and OCPs EMS None OD May cause N symptomatic and supportive... 

Miller WR, Bartlett J, Brodie AM, Brueggemeier RW, di Salle E, Lpnning PE, Llombart A, Maass N, Maudelonde T, Sasano H, Goss PE. Aromatase inhibitors are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter Oncologist 2008 13(8) 829-37. 

Chiral micellar solubilization may involve the use of chiral surfactants, or a combination of achiral surfactants and a chiral selector. Terabe [26] and Bereuter [25] provide a comprehensive overview of applications involving chiral surfactants such as bile salts or synthetic amino acid surfactants. The use of cyclodextrins (CD) as the chiral selector in combination with MEKC was successful for the separation of neutral racemic nonsteroidal aromatase inhibitors and barbituates [38]. Further approaches to the separation of enantiomers utilizing a combination of CD-MEKC have been described in the review by Terabe [26]. 

Breast cancer A selective nonsteroidal aromatase inhibitor Lactose, magnesium stearate, HPMC, PEG, povidone, sodium starch glycolate, titanium dioxide AstraZeneca... 

The nonsteroidal ttromatase inhibitors are competitive inhibitors that bind to the enzyme active site by coordinating the iron atom present in the heme group of the P-4S0 protein. Aside from aminoglutcthimidc. the first. selective aromatase inhibitor to be marketed in the United States was anastro/ole (Arimidex). Anastrozolc incorporates a triazole ring into its structure that can coordinate to the heme iron. Letrozolc is another triazolc-conuiining inhibitor that is also effective in the treatment of breast cancer. 

Vanden Bossche. H.V. er at. (1994) Aromatase inhibitors - mechanisms for nonsteroidal inhibitors. Breast Cancer Res. Treat.. 30.43-55. 

Recanatini M. Comparative molecular field analysis of nonsteroidal aromatase inhibitors related to fadrozole. J Comp Aided Mol Des 1996 10 74-82. 

Selective, nonsteroidal aromatase inhibitor inhibits conversion of androgens... 

Anastrozole is a selective nonsteroidal aromatase inhibitor, that lowers serum estradiol concentrations. It is indicated in advanced breast cancer in postmenopausal women with progression following tamoxifen therapy first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. 

However, fadrozole may now be surpassed by letro-zole (CGS20267 or Femara Figure 7.31), an advanced nonsteroidal aromatase inhibitor, which appears to be more potent and effective than fadrozole in the treatment of postmenopausal women with advanced breast cancer . 

Several other nonsteroidal compounds have been developed as novel and selective aromatase inhibitors, including 4-(4 -aminobenzyl)-2-oxazo-lidinones , 7-(alpha-azolylbenzyl)-lH-indoles and indolines of which l-ethyl-7-[(imidazol-l-yl) (4-chlorophenyl)methyl]-lH-indole 12c exhibited the most promising potency, 4-imidazolylfla-vans , and anastrozole (Arimidex Figure 7.31). Of these anastrozole has recently been approved in the United States and several other countries for... 

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