We have located links that may give you full text access.
Identification and Quantification of Novel Major Metabolites of the Steroidal Aromatase Inhibitor, Exemestane.
Drug Metabolism and Disposition : the Biological Fate of Chemicals 2018 September 27
Exemestane (EXE) is an aromatase inhibitor used for the prevention and treatment of estrogen receptor-positive breast cancer. Although the known major metabolic pathway for EXE is reduction to form the active 17β-dihydro-EXE (17β-DHE) and subsequent glucuronidation to 17β-hydroxy-EXE-17-O-β;-D-glucuronide (17β-DHE-Gluc), previous studies suggest that other major metabolites exist for exemestane. In the present study, a liquid chromatography-mass spectrometry (LC-MS) approach was used to acquire accurate mass data in MSE mode, in which precursor ion and fragment ion data was obtained simultaneously to screen novel phase II EXE metabolites in urine specimens from women taking EXE. Two major metabolites predicted to be cysteine conjugates of EXE and 17β-DHE by elemental composition were identified. The structures of the two metabolites were confirmed to be 6-methylcysteinylandrosta-1,4-diene-3,17-dione (6-EXE-cys) and 6-methylcysteinylandrosta-1,4-diene-17&#[beta]-hydroxy-3-one (6-17β-DHE-cys) after comparison to their chemically-synthesized counterparts. Both underwent biosynthesis in vitro in three stepwise enzymatic reactions with the first involving glutathione conjugation. The cysteine conjugates of EXE and 17β-DHE were subsequently quantified by LC-MS in the urine and matched plasma samples of 132 subjects taking EXE. The combined 6-EXE-cys plus 6-17β-DHE-cys made up 77% of total EXE metabolites in urine (versus 1.7, 1.4, and 21% for EXE, 17β-DHE, and 17β-DHE-Gluc, respectively) and 35% in plasma (versus 17, 12, and 36% for EXE, 17β-DHE, and 17β-DHE-Gluc, respectively). Therefore, cysteine conjugates of EXE and 17β-DHE appear to be major metabolites of EXE in both urine and plasma.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app