PMID: 11341362May 9, 2001Paper

Reversible binding of the novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid to plasma proteins and its distribution into blood cells in various species

The Journal of Pharmacy and Pharmacology
S ZhouM D Tingle

Abstract

The plasma protein binding and distribution in blood cells of the novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) has been investigated in-vitro using filtration and an HPLC method to measure DMXAA. DMXAA (500 microM) was extensively bound in plasma from all species with an unbound fraction (fu) of 4.61+/-1.10 (mouse), 2.59+/-0.32 (rat), 2.02+/-0.48 (rabbit) and 2.07+/-0.23% (human). The binding was concentration dependent with DMXAA concentrations > or = 1,000 microM markedly increasing the fu in the plasma from all species. The estimated number of binding sites in plasma were 2.4+/-0.2 (mouse), 1.7+/-0.2 (rat), 0.8+/-0.1 (rabbit) and 2.1+/- 0.2 (human). The major binding protein in human plasma was albumin, with negligible binding to gamma-globulin and alpha1-acid glycoprotein. There was a significant linear relationship between the bound:free DMXAA concentration ratio (Cb/Cu) and albumin concentration in human serum albumin solution (r = 0.955; P < 0.05) and in healthy human plasma (r = 0.998; P< 0.05), but not in plasma from cancer patients (n = 5), nor across species. In cancer patients (n = 5) DMXAA had a significantly higher (P < 0.05) fu (4.60+/- 0.42%) compared with healthy human plasma (2.07+/-0.2...Continue Reading

References

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Citations

Oct 6, 2006·Cancer Chemotherapy and Pharmacology·M B JamesonUNKNOWN Cancer Research (UK) Phase I/II Trials Committee
Feb 28, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shufeng ZhoJames W Paxton
Jul 26, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shufeng ZhouJames W Paxton
Jan 7, 2010·Expert Opinion on Investigational Drugs·Michelle Head, Michael B Jameson
Aug 30, 2011·Expert Opinion on Drug Metabolism & Toxicology·Michael B Jameson, Michelle Head
Jul 4, 2006·The Journal of Pharmacology and Experimental Therapeutics·Xiao-Xia YangShu-Feng Zhou
Sep 17, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael H LumpkinJeffrey W Fisher

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