Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA.
Cancer Chemother Pharmacol. 2011 Sep;68(3):593-601. doi: 10.1007/s00280-010-1525-4. Epub 2010 Nov 30.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring polyphenol with a broad range of possible health benefits, including anti-cancer activity. However, the biological activity of resveratrol may be limited by poor absorption and first-pass metabolism: only low plasma concentrations of resveratrol are seen following oral administration, and metabolism to glucuronide and sulfate conjugates is rapid. Methylated polyphenol analogs (such as pterostilbene [3,5-dimethoxy-4'-hydroxy-trans-stilbene], the dimethylether analog of resveratrol) may overcome these limitations to pharmacologic efficacy. The present study was designed to compare the bioavailability, pharmacokinetics, and metabolism of resveratrol and pterostilbene following equimolar oral dosing in rats.
The agents were administered orally via gavage for 14 consecutive days at 50 or 150 mg/kg/day for resveratrol and 56 or 168 mg/kg/day for pterostilbene. Two additional groups were dosed once intravenously with 10 and 11.2 mg/kg for resveratrol and pterostilbene, respectively. Plasma concentrations of agents and metabolites were measured using a high-pressure liquid chromatograph-tandem mass spectrometer system. Noncompartmental analysis was used to derive pharmacokinetic parameters.
Resveratrol and pterostilbene were approximately 20 and 80% bioavailable, respectively. Following oral dosing, plasma levels of pterostilbene and pterostilbene sulfate were markedly greater than were plasma levels of resveratrol and resveratrol sulfate. Although plasma levels of resveratrol glucuronide exceeded those of pterostilbene glucuronide, those differences were smaller than those of the parent drugs and sulfate metabolites.
When administered orally, pterostilbene demonstrates greater bioavailability and total plasma levels of both the parent compound and metabolites than does resveratrol. These differences in agent pharmacokinetics suggest that the in vivo biological activity of equimolar doses of pterostilbene may be greater than that of resveratrol.
白藜芦醇（3,5,4'-三羟基反式-二苯乙烯）是一种天然存在的多酚，具有广泛的潜在健康益处，包括抗癌活性。然而，白藜芦醇的生物活性可能受到吸收不良和首过代谢的限制：口服给药后，仅观察到低浓度的白藜芦醇在血浆中，并且迅速代谢为葡萄糖醛酸和硫酸盐缀合物。甲基化多酚类似物（如紫檀芪[3,5-二甲氧基-4'-羟基反式-二苯乙烯]，是白藜芦醇的二甲醚类似物）可能克服这些对药效的限制。本研究旨在比较等摩尔口服给药后白藜芦醇和紫檀芪的生物利用度、药代动力学和代谢。
将药物通过灌胃连续 14 天每天给予 50 或 150mg/kg 用于白藜芦醇和 56 或 168mg/kg 用于紫檀芪。另外两组分别静脉内给予 10 和 11.2mg/kg 的白藜芦醇和紫檀芪。使用高效液相色谱-串联质谱系统测量药物和代谢物的血浆浓度。使用非房室分析得出药代动力学参数。
白藜芦醇和紫檀芪的生物利用度分别约为 20%和 80%。口服给药后，紫檀芪和紫檀芪硫酸盐的血浆水平明显高于白藜芦醇和白藜芦醇硫酸盐的血浆水平。尽管白藜芦醇葡萄糖醛酸的血浆水平超过了紫檀芪葡萄糖醛酸的水平，但这些差异小于母体药物和硫酸盐代谢物的差异。
口服给予时，紫檀芪表现出比白藜芦醇更高的生物利用度和母体化合物及其代谢物的总血浆水平。这些药物药代动力学的差异表明，等摩尔剂量的紫檀芪的体内生物学活性可能大于白藜芦醇。
