Evaluation of liposomal curcumin cytochrome p450 metabolism.
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.


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 microM, 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.


CONCLUSIONS
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.
Mach
Claire M
CM
Department of Gynecologic Oncology, Division of Surgery, P.O. Box 301439-UNIT 1362, Houston, Texas 77230-1439, USA.
Chen
Jing Hong
JH
Mosley
Scott A
SA
Kurzrock
Razelle
R
Smith
Judith A
JA
D003474:Curcumin / Q000378:metabolism* / Q000493:pharmacokinetics; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008081:Liposomes / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D008081:Liposomes; D003577:Cytochrome P-450 Enzyme System; D003474:Curcumin