Evaluation of Liposomal Curcumin Cytochrome P450 Metabolism

被引:0
作者
Mach, Claire M. [2 ]
Chen, Jing Hong [3 ]
Mosley, Scott A. [1 ]
Kurzrock, Razelle [4 ]
Smith, Judith A. [1 ,3 ,5 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Div Surg, Houston, TX 77230 USA
[2] Univ Houston, Coll Pharm, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Div Pharm, Houston, TX 77230 USA
[4] Univ Texas MD Anderson Canc Ctr, Div Expt Therapeut, Houston, TX 77230 USA
[5] Univ Texas Hlth Sci Ctr Houston, Sch Med, Dept Obstet Gynecol & Reprod Sci, Houston, TX USA
关键词
Curcumin; cancer; metabolism; inhibitor; inducer; substrate; PANCREATIC-CANCER; APOPTOSIS; PROLIFERATION; INHIBITION; INDUCTION; PRODUCTS; TRIAL;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Curcumin (diferuloylmethane) is a commonly used spice and nutritional supplement that has demonstrated potential anti-tumor and anti-inflammatory activity. There is limited information regarding curcumin metabolism and the potential for drug-drug interactions. The objective of this study was to characterize the hepatic metabolism of synthetic curcumin used in the liposomal curcumin formulation. Materials and Methods: High-throughput cytochrome P450 (CYP450) metabolism inhibition_assays were conducted in vitro evaluating CYP450 3A4, 2C8, 2C9, and 2D6. An ex vivo model of cryopreserved human hepatocytes was used to evaluate the CYP450 metabolism induction potential of curcumin for CYP P450 3A4, 2C8/2C9, and 2D6. Results: In the in vitro CYP450 inhibition studies, curcumin at any concentration did not inhibit CYP450 3A4 or CYP450 2D6 activity. At a curcumin concentration of 58.3 mu M, 10.5% and 22.5% inhibition of CYP450 2C9 and CYP450 2C8 activity, respectively, was observed. In the ex vivo hepatocyte inductions studies, minimal to no induction of CYP450 3A4, CYP450 2C8/2C9 or CYP450 2D6 was observed. Rifampicin did not induce the metabolism of curcumin and curcumin did not induce its own metabolism. Conclusion: There is low potential for CYP450 mediated drug interactions at physiologic serum concentrations of liposomal curcumin. Based on preliminary data, liposomal curcumin will not interact with other chemotherapy agents that are metabolized and/or eliminated via the primary drug metabolizing CYP450 pathways.
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页码:811 / 814
页数:4
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