| Autor: |
Jennifer Witcher, Linda M. Rorick-Kehn, Conrad J. Wong, Gemma L. Dickinson, Celedon Gonzales, Randall Stoltz, Robert Bell, Stephen L. Lowe, Sitra Tauscher-Wisniewski, MaryAnn Weller, Jane Royalty |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
The Journal of Clinical Pharmacology. 54:968-978 |
| ISSN: |
0091-2700 |
| Popis: |
Accumulating evidence indicates that selective antagonism of kappa opioid receptors may provide therapeutic benefit in the treatment of major depressive disorder, anxiety disorders, and substance use disorders. LY2456302 is a high-affinity, selective kappa opioid antagonist that demonstrates >30-fold functional selectivity over mu and delta opioid receptors. The safety, tolerability, and pharmacokinetics (PK) of LY2456302 were investigated following single oral doses (2-60 mg), multiple oral doses (2, 10, and 35 mg), and when co-administered with ethanol. Plasma concentrations of LY2456302 were measured by liquid chromatography-tandem mass spectrometry method. Safety analyses were conducted on all enrolled subjects. LY2456302 doses were well-tolerated with no clinically significant findings. No safety concerns were seen on co-administration with ethanol. No evidence for an interaction between LY2456302 and ethanol on cognitive-motor performance was detected. LY2456302 displayed rapid oral absorption and a terminal half-life of approximately 30-40 hours. Plasma exposure of LY2456302 increased proportionally with increasing doses and reached steady state after 6-8 days of once-daily dosing. Steady-state PK of LY2456302 were not affected by coadministration of a single dose of ethanol. No clinically important changes in maximum concentration (Cmax ) or AUC of ethanol (in the presence of LY2456302) were observed. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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