Distribution and Metabolism of Lipocurc™ (Liposomal Curcumin) in Dog and Human Blood Cells: Species Selectivity and Pharmacokinetic Relevance
Distribution and Metabolism of Lipocurc™ (Liposomal Curcumin) in Dog and Human Blood Cells: Species Selectivity and Pharmacokinetic Relevance
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DOI：
10.21873/anticanres.11716
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发表时间：
2017-07-01
影响因子：
2
通讯作者：
Helson, Lawrence
中科院分区：
文献类型：
--
作者：
Bolger, Gordon T.;Licollari, Albert;Helson, Lawrence
背景/目的：研究姜黄素(以Lipocurc(TM)形式存在)及其主要代谢物四氢姜黄素(THC)在Beagle犬和人红细胞、外周血单核细胞(PBMC)和肝细胞中的分布。材料和方法：以Lipocurc(TM)为姜黄素的来源，进行细胞分布测定。红血球的体外研究结果也与狗的临床前研究和人类的I期临床研究的体内药代动力学数据进行了比较。结果：外周血单核细胞中姜黄素含量较高(625.5 ng/gW.w)。狗的细胞颗粒或7,297pg/10(6)细胞和353.7 ng/g W.W.细胞颗粒或6,809pg/10(6)细胞)和肝细胞(414.5 ng/gW.W.狗的细胞颗粒或14,005 pg/10(6)个细胞和813.5 ng/g W.W.细胞颗粒或13,780 pg/10(6)人细胞)。在红细胞中测得较低的姜黄素水平(狗：78.4 ng/g W.w。细胞颗粒或7.2pg/10(6)细胞，人：201.5 ng/gW.W.细胞颗粒或18.6pg/10(6)细胞)。红细胞和肝细胞中姜黄素浓度降低，而外周血单核细胞中姜黄素浓度无明显变化。狗的THC的红细胞水平比人高5倍，而肝细胞和PBMC的水平与人相似。犬红细胞培养上清液中THC与姜黄素的比值为6.3%，人为0.006，而PBMC和肝细胞中THc与姜黄素的比值没有明显的物种差异。结论：姜黄素和THC与红细胞孵育后的体外释放与犬和人静脉输注后的体内血浆中姜黄素和THC的浓度具有良好的相关性。因此，姜黄素在血细胞中的分布与物种有关，并与药代动力学有关。
Background/Aim: The aim of this study was to investigate the distribution of curcumin (in the form of Lipocurc (TM)) and its major metabolite tetrahydrocurcumin (THC) in Beagle dog and human red blood cells, peripheral blood mononuclear cells (PBMC) and hepatocytes. Materials and Methods: Lipocurc (TM) was used as the source of curcumin for the cell distribution assays. In vitro findings with red blood cells were also compared to in vivo pharmacokinetic data available from preclinical studies in dogs and phase I clinical studies in humans. Results: High levels of curcumin were measured in PBMCs (625.5 ng/g w.w. cell pellet or 7,297 pg/10(6) cells in dog and 353.7 ng/g w.w. cell pellet or 6,809 pg/10(6) cells in human) and in hepatocytes (414.5 ng/g w.w. cell pellet or 14,005 pg/10(6) cells in dog and 813.5 ng/g w.w. cell pellet or 13,780 pg/10(6) cells in human). Lower curcumin levels were measured in red blood cells (dog: 78.4 ng/g w.w. cell pellet or 7.2 pg/10(6) cells, human: 201.5 ng/g w.w. cell pellet or 18.6 pg/10(6) cells). A decrease in the medium concentration of curcumin was observed in red blood cells and hepatocytes, but not in PBMCs. Red blood cell levels of THC were similar to 5-fold higher in dog compared to human and similar between dog and human for hepatocytes and PBMCs. The ratio of THC to curcumin found in the red blood cell medium following incubation was 6.3 for dog compared to 0.006 for human, while for PBMCs and hepatocytes the ratio of THC to curcumin in the medium did not display such marked species differences. Conclusion: There was an excellent correlation between the in vitro disposition of curcumin and THC following incubation with red blood cells and in vivo plasma levels of curcumin and THC in dog and human following intravenous infusion. The disposition of curcumin in blood cells is, therefore, species-dependent and of pharmacokinetic relevance.