The random effects were in cluded to account for the auto correlation of residuals in the extent of bioavailability across the different curcu min formulations in the same subjects. Plasma concen trations of all curcuminoids k measured for the individual subject i at each time sam pling hour Erlotinib mechanism of action j was further characterized into a vector Ckij with the curcumin formulations compared in separate levels over the duration of the study. Mean plasma concentration Inhibitors,Modulators,Libraries time curves were obtained by tak ing the antilogarithm of the mean predicted plasma con centration Inhibitors,Modulators,Libraries during each time point for the individual curcuminoids across the formulations. The cmax was the maximum observed plasma concentration directly from the mean plasma concentration time profile and the Area Under the Plasma Concentration Time Curve was calculated by the definite integral from 0 12 hours of the mean plasma concentration time curves.

Calculation of t? could not take place as a number of the formulations Inhibitors,Modulators,Libraries did not decline in concentration over the 12 hour time period. Results Absorption of curcumin, demethoxycurcumin, bisdeme thoxycurcumin, and appearance in the blood of tetrahy drocurcumin was measured in 12 healthy volunteers in a randomized, double blind, crossover study. The subjects consumed either 376 mg of total curcumi noids in the form of CP, CTR, or CHC, or 1,800 mg of the corresponding non formulated CS in accordance with Cuomo et al. Since free curcumin could not be detected in previous studies, even at levels of up to 12,000 mg, plasma samples were treated with Helix pomatia glucuronidase sulfatase before HPLC MS MS analysis.

All four treatments were well tolerated and no adverse events were reported. Pharmacokinetic data of the individual curcuminoids for the formulation were Inhibitors,Modulators,Libraries each plotted on a plasma con centration vs. time curve. Area Under the Plasma Concentration Time Curve, cmax, tmax and relative absorption were calculated for each curcuminoid at all levels of the formulations and are presented in Table 1. The relative absorption was calcu lated by dividing the value of test product by the value of reference product multiplied by Inhibitors,Modulators,Libraries the dosage of the reference product divided by dosage of the test product. There were significant differences between the time of maximum plasma concentrations of the four products as shown by the results of a nonparametric Friedmans Test. Post hoc tests of a Wilcoxon Signed Rank Test displayed that CTR had a significantly higher tmax in comparison to CP. Relative total curcuminoid appearance was 7. 9 fold higher for CP in comparison to the unformulated Fluoro Sorafenib CS product. CHC showed a 45. 9 fold higher relative ap pearance over standard and was significantly improved over CS, CP and CTR.