Meganathan Puvaneswari, Jabir Rafid Salim, Fuang Ho Gwo, Bhoo-Pathy Nirmala, Choudhury Roma Basu, Taib Nur Aishah, Nesaretnam Kalanithi, Chik Zamri
Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Sci Rep. 2015 Sep 1;5:13550. doi: 10.1038/srep13550.
Gamma and delta tocotrienols are isomers of Vitamin E with established potency in pre-clinical anti-cancer research. This single-dose, randomized, crossover study aimed to compare the safety and bioavailability of a new formulation of Gamma Delta Tocotrienol (GDT) in comparison with the existing Tocotrienol-rich Fraction (TRF) in terms of gamma and delta isomers in healthy volunteers. Subjects were given either two 300 mg GDT (450 mg γ-T3 and 150 mg δ-T3) capsules or four 200 mg TRF (451.2 mg γ-T3 &102.72 mg δ-T3) capsules and blood samples were taken at several time points over 24 hours. Plasma tocotrienol concentrations were determined using HPLC method. The 90% CI for gamma and delta tocotrienols for the ratio of log-transformation of GDT/TRF for Cmax and AUC0-∞ (values were anti-logged and expressed as a percentage) were beyond the bioequivalence limits (106.21-195.46, 154.11-195.93 and 52.35-99.66, 74.82-89.44 respectively). The Wilcoxon Signed Rank Test for Tmax did not show any significant difference between GDT and TRF for both isomers (p > 0.05). No adverse events were reported during the entire period of study. GDT was found not bioequivalent to TRF, in terms of AUC and Cmax. Gamma tocotrienol in GDT showed superior bioavailability whilst delta tocotrienol showed less bioavailability compared to TRF.
γ-和δ-生育三烯酚是维生素E的异构体，在临床前抗癌研究中已证实具有一定效能。这项单剂量、随机、交叉研究旨在比较一种新型γ-δ生育三烯酚（GDT）制剂与现有的富含生育三烯酚组分（TRF）在健康志愿者体内γ-和δ-异构体方面的安全性和生物利用度。受试者分别服用两粒300毫克GDT（450毫克γ-T3和150毫克δ-T3）胶囊或四粒200毫克TRF（451.2毫克γ-T3和102.72毫克δ-T3）胶囊，并在24小时内的多个时间点采集血样。使用高效液相色谱法测定血浆生育三烯酚浓度。GDT/TRF的Cmax和AUC0-∞对数转换比值的γ-和δ-生育三烯酚的90%置信区间（数值进行反对数转换并以百分比表示）超出了生物等效性限度（分别为106.21 - 195.46、154.11 - 195.93和52.35 - 99.66、74.82 - 89.44）。Tmax的Wilcoxon符号秩检验显示，两种异构体在GDT和TRF之间均未显示出任何显著差异（p>0.05）。在整个研究期间未报告不良事件。就AUC和Cmax而言，发现GDT与TRF不具有生物等效性。与TRF相比，GDT中的γ-生育三烯酚显示出更高的生物利用度，而δ-生育三烯酚显示出较低的生物利用度。
