1698

Curcumin, the major polyphenolic antioxidant present in the herb Curcuma longa exhibits anticancer activity in rodents and humans. We designed a clinical trial to 1) to determine if curcumin in a capsule formulation is absorbed, and 2) to assess the pharmacokinetics (PK) of curcumin in healthy human subjects. The trial was performed in two groups of six healthy human subjects 0.5-72 hours after administering 10 or 12 g curcumin as a single dose. A reverse-phase gradient HPLC method was developed for identifying and quantifying curcumin in plasma. The assay was linear from 0.075 to 10µg/mL. Since free curcumin was detected in only one subject at one time point, serum samples were assayed after deconjugation of the glucuronide and sulfate metabolites of curcumin. All the curcumin in plasma was conjugated, and enzymatic hydrolysis was necessary to quantify curcumin. The maximal concentration of the conjugated forms was achieved 2-10 h after oral administration with a concentration range of 1.1-3.7 μg/mL. The data were fit to a one-compartment model with first order absorption and elimination using NONMEM. PK is shown in Table below. Fixed effect parameter estimates indicated an absorption lag time of 40mins and an absorption half life of 1.4 hours. CL/F and Vd/F were estimated to be 476L/hr and 2550L, respectively. Between subject variability estimates (as percent coefficient of variation) in CL/F and Ka were 61% and 89%, respectively. Since all of the detectable forms of curcumin after oral dosing are in the conjugated form, we speculate that the reported systemic biologic activity of oral curcumin in preclinical models may be due to its circulating conjugates. [Supported by: NCI-N01-CN-35160 and AICR#06A035.]

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA