La curcumina, composto attivo del rizoma di curcuma longa ha un’azione inibente nei confronti del citocromo P450 ossia degli enzimi di Fase I del fegato deputati all’eliminazione di sostanze non organiche, come tossine, polifenoli delle piante e soprattutto farmaci, quindi inibire questi enzimi in concomitanza dell’utilizzo di farmaci può risultare pericoloso in quanto quote maggiori di farmaco possono entrare in circolo rispetto alla dose voluta. Perciò bisogna fare attenzione al tipo di curcuma che si utilizza.
Drug Dev Ind Pharm. 2015 Apr;41(4):613-6. doi: 10.3109/03639045.2014.886697. Epub 2014 Feb 12.
Inhibitory effects of curcumin on activity of cytochrome P450 2C9 enzyme in human and 2C11 in rat liver microsomes.
Cytochrome P450 2C9 (CYP2C9), one of the most important phase I drug metabolizing enzymes, could catalyze the reactions that convert diclofenanc into diclofenac 4′-hydroxylation. Evaluation of the inhibitory effects of compounds on CYP2C9 is clinically important because inhibition of CYP2C9 could result in serious drug-drug interactions. The objective of this work was to investigate the effects of curcumin on CYP2C9 in human and cytochrome P450 2C11 (CYP2C11) in rat liver microsomes. The results showed that curcumin inhibited CYP2C9 activity (10 µmol L(-1) diclofenac) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 15.25 µmol L(-1) and Ki = 4.473 µmol L(-1) in human liver microsomes. Curcumin’s mode of action on CYP2C9 activity was noncompetitive for the substrate diclofenanc and uncompetitive for the cofactor NADPH. In contrast to its potent inhibition of CYP2C9 in human, diclofenanc had lesser effects on CYP2C11 in rat, with an IC50 ≥100 µmol L(-1). The observations imply that curcumin has the inhibitory effects on CYP2C9 activity in human. These in vitro findings suggest that more attention should be paid to special clinical caution when intake of curcumin combined with other drugs in treatment:
Le forme complessate con liposomi o fosfolipidi invece non interagiscono col citocromo, in quanto entra nel fegato, di fatto una molecola organica, un grasso o un fosfolipide, pertanto non vi sono interazioni con l’uso di curcuma liposomata o fosfolipata e farmaci, lo studio sottostante dimostra appunto che non vi sono interazioni tra curcuma liposomata e agenti chemioterapici.
Anticancer Res. 2010 Mar;30(3):811-4.
Evaluation of liposomal curcumin cytochrome p450 metabolism.
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.
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.
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.