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Randomized Controlled Trial
. 2008 Jun;17(6):1411-7.
doi: 10.1158/1055-9965.EPI-07-2693.

Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects

Shaiju K Vareed  1 , Madhuri Kakarala, Mack T Ruffin, James A Crowell, Daniel P Normolle, Zora Djuric, Dean E Brenner
Affiliations
Randomized Controlled Trial

Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects

Shaiju K Vareed et al. Cancer Epidemiol Biomarkers Prev. 2008 Jun.

Abstract

Background: Curcumin is a polyphenol, found in the spice turmeric, that has promising anticancer properties, but previous studies suggest that absorption of curcumin may be limited.

Methods: This study examined the pharmacokinetics of a curcumin preparation in healthy human volunteers 0.25 to 72 h after a single oral dose. Curcumin was administered at doses of 10 g (n = 6) and 12 g (n = 6). Subjects were randomly allocated to dose level for a total of six subjects at each dose level. Serum samples were assayed for free curcumin, for its glucuronide, and for its sulfate conjugate. The data were fit to a one-compartment absorption and elimination model.

Results: Using a high-performance liquid chromatography assay with a limit of detection of 50 ng/mL, only one subject had detectable free curcumin at any of the 14 time points assayed, but curcumin glucuronides and sulfates were detected in all subjects. Based on the pharmacokinetic model, the area under the curve for the 10 and 12 g doses was estimated (mean +/- SE) to be 35.33 +/- 3.78 and 26.57 +/- 2.97 mug/mL x h, respectively, whereas C(max) was 2.30 +/- 0.26 and 1.73 +/- 0.19 mug/mL. The T(max) and t(1/2) were estimated to be 3.29 +/- 0.43 and 6.77 +/- 0.83 h. The ratio of glucuronide to sulfate was 1.92:1. The curcumin conjugates were present as either glucuronide or sulfate, not mixed conjugates.

Conclusion: Curcumin is absorbed after oral dosing in humans and can be detected as glucuronide and sulfate conjugates in plasma.

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Figures

Fig. 1
Fig. 1
Structures of curcumin (I), curcumin glucuronide (II) and curcumin sulfate (III).
Fig. 2
Fig. 2
HPLC chromatograms of extracted plasma 1 hour after a 12 g dose of curcumin. The plasma was analyzed without incubation (A) and after incubation with β-glucuronidase (440 units) and aryl sulfatase (50 units) for 3.5 h (B).
Fig. 3
Fig. 3
Modeled time concentration plots of curcumin conjugates detected in plasma from 12 human subjects treated with a single 10 g (A) or 12 g (B) dose with confidence interval depicted in gray.
See this image and copyright information in PMC

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