Pharmacokinetics and tissue distribution of inositol hexaphosphate in C.B17 SCID mice bearing human breast cancer xenografts

Inositol hexaphosphate (IP6) is effective in preclinical cancer prevention and chemotherapy. In addition to cancer, IP6 has many other beneficial effects for human health, such as reduction in risk of developing cardiovascular disease and diabetes and inhibition of kidney stone formation. Studies presented here describe the pharmacokinetics, tissue distribution, and metabolism of IP6 following intravenous (IV) or per os (PO) administration to mice. SCID mice bearing MDA-MB-231 xenografts were treated with 20 mg/kg IP6 (3 mu Ci per mouse uniformly ring-labeled IP6) and euthanized at various times after IP6 treatment. Plasma and tissues were analyzed for [C-14]-IP6 and metabolites by high-performance liquid chromatography with radioactivity detection. Following IV administration of IP6, plasma IP6 concentrations peaked at 5 minutes and were detectable until 45 minutes. Liver IP6 concentrations were more than 10-fold higher than plasma concentrations, whereas other normal tissue concentrations were similar to plasma. Only inositol was detected in xenografts. After PO administration, IP6 was detected in liver; but only inositol was detectable in other tissues. After both IV and PO administration, exogenous IP6 was rapidly dephosphorylated to inositol; however, alterations in endogenous IPs were not examined. (C) 2011 Elsevier Inc. All rights reserved.