Pharmacokinetics and bioavailability of α-, γ- and δ-tocotrienols under different food status

We have investigated the pharmacokinetics and bioavailability of alpha-, gamma- and delta -tocotrienols under fed and fasted conditions in eight healthy volunteers. The volunteers were administered a single oral dose of mixed tocotrienols (300 mg) under fed or fasted conditions. The bioavailability of tocotrienols under the two conditions was compared using the parameters peak plasma concentration (C-max), time to reach peak plasma concentration (T-max) and total area under the plasma concentration-time curve (AUC(0-infinity)). A statistically significant difference was observed between the fed and fasted logarithmic transformed values of C-max (P < 0.01) and AUC(0-<infinity>) (P < 0.01) for all three tocotrienols. In addition, the 90% confidence intervals for the ratio of the logarithmic transformed AUC(0-<infinity>) values of alpha-, gamma- and delta -tocotrienols under the fed state over those of the fasted state were found to lie between 2.24-3.40, 2.05-4.09 and 1.59-3.81, respectively, while those of the C-max were between 2.28-4.39, 2.31-5.87 and 1.52-4.05, respectively. However, no statistically significant difference was observed between the fed and fasted T-max values of the three homologues. The mean apparent elimination half-life (t(1/2)) of alpha-, gamma- and delta -tocotrienols was estimated to be 4.4, 4.3 and 2.3 h, respectively, being between 4.5- to 8.7-fold shorter than that reported for alpha -tocopherol. No statistically significant difference was observed between the fed and fasted t(1/2) values. The mean apparent volume of distribution (Vd/f) values under the fed state were significantly smaller than those of the fasted state, which could be attributed to increased absorption of the tocotrienols in the fed state.