Pharmacokinetics of Curcumin Conjugate Metabolites in Healthy Human Subjects

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 17; no. 6; pp. 1411 - 1417
• Main Authors: Vareed, Shaiju K., Kakarala, Madhuri, Ruffin, Mack T., Crowell, James A., Normolle, Daniel P., Djuric, Zora, Brenner, Dean E.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.2008
• Subjects: Administration, Oral; Adolescent; Adult; Aged; Area Under Curve; Biological and medical sciences; Chemoprevention; Chromatography, High Pressure Liquid; Clinical trial; Curcumin; Curcumin - administration & dosage; Curcumin - pharmacokinetics; Female; Glucuronides - blood; Humans; Male; Medical sciences; Metabolism; Middle Aged; Pharmacokinetics; Sulfates - blood; Time Factors; Tumors; Human; Polyphenol; Cancerology; Healthy subject; Metabolite; Phenols; Curcumin; Conjugated compound; Pharmacokinetics
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-07-2693

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 μg/mL × h, respectively, whereas C max was 2.30 ± 0.26 and 1.73 ± 0.19 μg/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. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1411–7)