תשובתו של קונסטנטין קניקילידיס, חוקר של סרטן השד, בפורום "סרטן שד"
AIs, letrozole (Femara) strongly inhibits CYP2A6, moderately inhibits CYP2C19, and has a low affinity for CYP3A4; exemestane (Aromasin) is metabolized by CYP3A4, and anastrozole (Arimidex) metabolism is in part CYP1A1/2, CYP2B1, CYP2C9, and CYP3A4-mediated.
The metabolism and pharmacokinetics of the aromatase inhibitors (AIs) show the well-know potential dependency on the p450 hepatic (liver) enzyme system, especially with CYP3A4, and to a lesser extent CYP1A1 and CYP2B1-mediation. But although curcumin can theoretically induce CYP3A4 in human hepatocytes, it been determined by Judy Raucy of the California Toxicology Research Institute (Raucy, Drug Metab Dispos (2003): Regulation of CYP3A4 Expression in Human Hepatocytes by Pharmaceuticals and Natural Products) that curcumin lacks clinically significant (true in vivo) CYP3A4 activity, and hence it lacks potential adverse CYP3A4-mediated interactions.
Secondly, although curcumin also displays CYP1A1 and CYP2B1-mediated metabolism and anastrozole (Arimidex) is a CYP1A1-mediated AI agent, for complex reasons having to do with substrates and metabolites, when curcumin is co-administered with such agents, the effect is of increasing the bioavailability of curcumin, not of reducing the effect of the interacting agent, and increased curcumin bioavailability is unproblematic as curcumin has been demonstrated to be safe even up to 12 grams/daily. Finally, although anastrozole Arimidex metabolism is also in part CYP1A2, CYP2C9, and CYP3A4-mediated in addition to CYP1A1 and CYP2B1), and carries an FDA labeling warning to that effect, the FDA concludes – in the same warning – that these dependencies exist but only at relatively high concentrations in vitro and therefore that it is unlikely that co-administration of (a 1-mg dose) of Arimidex with other drugs would result in any clinically significant drug inhibition in vivo, and my own research confirms this (as per AstraZenica scientists Scott Grimm and Martin Dyroff's determination (Drug Matab Dispos (1999): Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase) who concluded that Arimidex would not be expected to cause clinically significant interactions with other CYP-metabolized drugs at physiologically relevant concentrations achieved during therapy with Arimidex); and I determined that this is further confirmed by Masha Lam and Robert Ignoffo in their comprehensive review (J Oncol Pharm Pract (2003): A guide to clinically relevant drug interactions in oncology).
In sum therefore, curcumin coadministration with any AI is unproblematic in terms of any potential adverse metabolic interaction or pharmacokinetics, and no adverse interactions have appeared to date for curcuminin in general.
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