Can Curcuma longa (English: Turmeric, Swedish: gurkmeja) cause increased tacrolimus levels?/nA 36-y

Fråga: Can Curcuma longa (English: Turmeric, Swedish: gurkmeja) cause increased tacrolimus levels? A 36-year-old man with a renal transplant is treated with tacrolimus, mycophenolate mofetil, prednisolone, omeprazole and losartan. His tacrolimus blood levels have been stable around 6 ng/mL for several months. After visiting a friend over the week-end eating healthy foods including oriental spices such as turmeric his tacrolimus level was 27 ng/mL. Analysis with a chromatographic method verified that the concentration of tacrolimus parent substance was above 20 ng/mL. No diarrhoea, no infection, no hepatic failure.

Sammanfattning: It cannot be excluded that a relatively high dietary intake or claimed pharmacological doses of Curcuma species may interact with tacrolimus and other CYP3A4 substrates. In the particular case, however, it is possible that other factors may be involved as well.

Svar: Curcuma species have been claimed to have several pharmacological effects (e.g. antitumoural, anti-inflammatory, digestive) based on animal studies and traditional use (1).

Extracts of Curcuma longa have been shown to have some pharmacological properties in animals and isolated organs (2). In an in vitro experiment methanol extracts of Curcuma longa was shown to inhibit CYP3A4 with an IC50 of around 0.02 g/L (3). Based on the 15% yield of the extraction method, this is equivalent to 0.13 g/L of Curcuma powder. The effect of Curcuma on transport proteins such as Pgp has not been studied.

Since the suggested pharmacological dose of Curcuma is 1-3 g daily, it is not impossible to get an intraluminal concentration of Curcuma in the intestine around or above 0.13 g/L at least for some time after ingestion. A little experiment performed by the author showed that 1 teaspoon (5 mL) of turmeric powder weighs 2.3 g. Thus suggested pharmacological doses are not far from the possible exposure by an oriental meal.

Tacrolimus is subject to substantial first pass metabolism with an oral bioavailability of 20-25% (4) and so it is not impossible that high doses of Curcuma may increase systemic availability of this immunosuppressant. Since Curcuma extracts seem to diminish CYP3A4 protein without interfering with transcription (3), it is possible that the decrease in CYP3A4 metabolic capacity may last for a week or so.

As always, however, it is difficult to extrapolate in vitro findings to the in vivo situation.