Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

McKeage, M.J. et al.

Plasma pharmacokinetics of the antitumour agents 5,6-dimethylxanthenone-4-acetic acid, xanthenone-4-acetic acid and flavone-8-acetic acid in mice.

Although the antitumour agent flavone-8-acetic acid (FAA) exhibits remarkable activity against murine solid tumours, its clinical use has a number of pharmacological drawbacks, including low dose potency and dose-dependent pharmacokinetics. Xanthenone-4-acetic acid (XAA) and its 5,6-dimethyl derivative (5,6-MeXAA) were synthesised during a search for better analogues of FAA. The maximal tolerated doses (MTDs) of 5,6-MeXAA, XAA and FAA in BDF1 mice were 99, 1,090 and 1,300 mumol/kg, respectively. At the MTD, 5,6-MeXAA displayed the following pharmacokinetic properties: maximal plasma concentration, 600 microM; mean residence time, 4.9 h; AUC, 2,400 mumol h 1-1; and volume of steady-state distribution, 0.2 l/kg. All compounds displayed nonlinear elimination kinetics at the MTD, but when the logarithm of the AUC was plotted against that of the delivered dose, the slope of the regression line for 5,6-MeXAA was found to be 1.2 as opposed to 1.4 for XAA and 1.98 for FAA. 5,6-MeXAA thus showed only a slight deviation from dose-independent kinetics. 5,6-MeXAA bound to plasma proteins in a manner similar to that exhibited by FAA, although the plasma concentration of free drug was lower for the former than for the latter. As a consequence, the calculated maximal free drug concentration for 5,6-MeXAA in plasma was 23 times lower than that for FAA.[1]

References

Plasma pharmacokinetics of the antitumour agents 5,6-dimethylxanthenone-4-acetic acid, xanthenone-4-acetic acid and flavone-8-acetic acid in mice. McKeage, M.J., Kestell, P., Denny, W.A., Baguley, B.C. Cancer Chemother. Pharmacol. (1991) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.