Bazedoxifene, a selective estrogen receptor modulator, has been explicitly included in the prohibited list issued by the World Anti-Doping Agency (WADA) since January 2020. A high-resolution liquid chromatography-tandem mass spectrometric detection method was developed to identify bazedoxifene and its metabolites in human urine and to quantify bazedoxifene (free plus glucuronide) for doping control purposes. Bazedoxifene acetate (20 mg) was orally administered to seven male volunteers, and the urine samples collected were analyzed using the developed method. The linearity ranged from 0.5 to 200 ng/ml, and the limit of detection was <0.2 ng/ml. The interday precision (2.2% to 3.6%) and the interday accuracy (-10.0% to 1.9%) were adequate. Bazedoxifene, bazedoxifene-N-oxide, and bazedoxifene glucoconjugates were identified in the urine samples. The profiles of the urinary excretion indicated the presence of small amounts of free bazedoxifene and bazedoxifene-N-oxide, whereas bazedoxifene glucuronide was the predominant metabolite. The cumulative excretion amount of bazedoxifene (free form plus glucuronide conjugate) within 78 h after the administration was 0.7% to 1.3% of the total dose. In all subjects, bazedoxifene (free plus glucuronide) could be detected in urine up to 78 h after administration.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/dta.3225 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integrating traditional QSAR and read-across-based regression models for predicting potential anti-leishmanial azole compounds.
Mol Divers
December 2024
Deparment of Microbiology, Assam University, Silchar, 788011, Assam, India.
Leishmaniasis, a neglected tropical disease caused by various Leishmania species, poses a significant global health challenge, especially in resource-limited regions. Visceral Leishmaniasis (VL) stands out among its severe manifestations, and current drug therapies have limitations, necessitating the exploration of new, cost-effective treatments. This study utilized a comprehensive computational workflow, integrating traditional 2D-QSAR, q-RASAR, and molecular docking to identify novel anti-leishmanial compounds, with a focus on Glycyl-tRNA Synthetase (LdGlyRS) as a promising drug target.
View Article and Find Full Text PDFPolypharmacological profiling across protein target families and cellular pathways using the multiplexed cell-based assay platform safetyProfiler reveals efficacy, potency and side effects of drugs.
Biomed Pharmacother
November 2024
Research Group Cell Signalling, Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstr. 7, Munich 80336, Germany; Systasy Bioscience GmbH, Fraunhoferstr. 8, Planegg-Martinsried 82152, Germany. Electronic address:
Selectivity profiling is key for assessing the pharmacological properties of multi-target drugs. We have developed a cell-based and barcoded assay encompassing ten druggable targets, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), nuclear receptors, a protease as well as their key downstream pathways and profiled 17 drugs in living cells for efficacy, potency, and side effects. Notably, this multiplex assay, termed safetyProfiler assay, enabled the simultaneous assessment of multiple target and pathway activities, shedding light on the polypharmacological profile of compounds.
View Article and Find Full Text PDFOvercoming challenges in conducting early phase breast cancer prevention trials: Bazedoxifene and conjugated estrogens vs waitlist control.
Contemp Clin Trials
November 2024
University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Background: The combination of bazedoxifene 20 mg (BZA) and conjugated estrogens 0.45 mg (CE) marketed as Duavee® is approved for vasomotor symptom relief and osteoporosis prevention. Our pilot study suggested it had potential breast cancer risk reduction, and we proposed a multisite Phase IIB primary prevention trial assessing change in breast imaging and tissue risk biomarkers.
View Article and Find Full Text PDFStructurally diverse design and synthesis of novel 2-phenylindole amide derivatives with anti-canine breast cancer activity.
Bioorg Chem
December 2024
Natural Medicine Research Center, Pharmacy department, Sichuan Agricultural University, Chengdu 611130, PR China.
Breast cancer stands as the cancer with the highest incidence and mortality rates among women globally, in which triple-negative breast cancer has been ranked as the most difficult one. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), has been exhibited notable inhibitory effect on both hormone-dependent breast cancer cells and triple-negative breast cancer cells, but showing very low in vivo effeacy. In order to obtain more effective antitumor derivatives than BZA, we have employed a structurally diverse design and synthesis of 57 novel 2-phenylindole amides for detecting their cytotoxities against triple-negative mammary cancer cell line, CMT-7364.
View Article and Find Full Text PDFHormonal Treatments and Vaginal Moisturizers for Genitourinary Syndrome of Menopause : A Systematic Review.
Ann Intern Med
October 2024
Center for Care Delivery & Outcomes Research, VA Health Care System, and Department of Medicine, University of Minnesota, Minneapolis, Minnesota (E.R.D., S.D.).
Background: Postmenopausal women commonly experience vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM).
Purpose: To evaluate effectiveness and harms of vaginal estrogen, nonestrogen hormone therapies, and vaginal moisturizers for treatment of GSM symptoms.
Data Sources: Medline, Embase, and CINAHL through 11 December 2023.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!