Molecular Therapeutics and Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Metabolism. 2011 Oct;60(10):1465-74. doi: 10.1016/j.metabol.2011.02.015. Epub 2011 Apr 12.
Inositol hexaphosphate (IP(6)) is effective in preclinical cancer prevention and chemotherapy. In addition to cancer, IP(6) 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 IP(6) following intravenous (IV) or per os (PO) administration to mice. SCID mice bearing MDA-MB-231 xenografts were treated with 20 mg/kg IP(6) (3 μCi per mouse [(14)C]-uniformly ring-labeled IP(6)) and euthanized at various times after IP(6) treatment. Plasma and tissues were analyzed for [(14)C]-IP(6) and metabolites by high-performance liquid chromatography with radioactivity detection. Following IV administration of IP(6), plasma IP(6) concentrations peaked at 5 minutes and were detectable until 45 minutes. Liver IP(6) 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, IP(6) was detected in liver; but only inositol was detectable in other tissues. After both IV and PO administration, exogenous IP(6) was rapidly dephosphorylated to inositol; however, alterations in endogenous IPs were not examined.
肌醇六磷酸（IP(6)）在癌症的临床前预防和化疗中非常有效。除了癌症之外，IP(6)对人类健康还有许多其他有益的影响，例如降低患心血管疾病和糖尿病的风险以及抑制肾结石形成。本文介绍了静脉内（IV）或口服（PO）给予小鼠后 IP(6)的药代动力学、组织分布和代谢。在 MDA-MB-231 异种移植的 SCID 小鼠中，给予 20mg/kg IP(6)（每只小鼠 3μCi [14C]-均环标记的 IP(6)），并在 IP(6)处理后不同时间处死。通过放射性检测的高效液相色谱法分析血浆和组织中的[14C]-IP(6)和代谢物。静脉内给予 IP(6)后，血浆 IP(6)浓度在 5 分钟时达到峰值，直至 45 分钟仍可检测到。肝 IP(6)浓度比血浆浓度高 10 多倍，而其他正常组织浓度与血浆相似。仅在异种移植物中检测到肌醇。口服给药后，在肝脏中检测到 IP(6)；但在其他组织中仅可检测到肌醇。静脉内和口服给药后，外源性 IP(6)迅速被去磷酸化为肌醇；然而，未检查内源性 IP 的变化。
