Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats.
Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats.
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白藜芦醇的药代动力学，口服生物利用度和代谢概况及其二甲基类似物，翼龙，大鼠。
DOI：
10.1007/s00280-010-1525-4
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发表时间：
2011-09
影响因子：
3
通讯作者：
McCormick, David L.
中科院分区：
文献类型：
--
作者：
Kapetanovic, Izet M.;Muzzio, Miguel;Huang, Zhihua;Thompson, Thomas N.;McCormick, David L.
白藜芦醇（3，5，4 ′-三羟基-反式-芪）是一种天然存在的多酚，具有广泛的健康益处，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血浆浓度的白藜芦醇，并且代谢为葡萄糖醛酸苷和硫酸盐结合物是快速的。甲基化多酚类似物（如紫檀芪[3，5-二甲氧基-4 ′-羟基-反式-芪]，白藜芦醇的二甲醚类似物）可以克服这些药理学功效的限制。本研究旨在比较白藜芦醇和紫檀芪等摩尔口服给药后的生物利用度，药代动力学和代谢。通过管饲法连续14天口服给予试剂，白藜芦醇为50或150 mg/kg/天，紫檀芪为56或168 mg/kg/天。另外两个组分别以10和11.2 mg/kg的白藜芦醇和紫檀芪静脉内给药一次。使用高压液相色谱-串联质谱仪系统测量药物和代谢物的血浆浓度。采用非房室分析推导药代动力学参数。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，紫檀芪和硫酸紫檀芪的血浆水平显著高于白藜芦醇和硫酸白藜芦醇的血浆水平。虽然白藜芦醇葡萄糖醛酸苷的血浆水平超过紫檀芪葡萄糖醛酸苷，但这些差异小于母体药物和硫酸盐代谢产物的差异。当口服给药时，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和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活性可能大于白藜芦醇。
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.
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影响因子：
7.3
作者：
Hoshino J;Park EJ;Kondratyuk TP;Marler L;Pezzuto JM;van Breemen RB;Mo S;Li Y;Cushman M
通讯作者：
Cushman M
DOI：
10.1124/jpet.102.033340
发表时间：
2002-07-01
影响因子：
3.5
作者：
Marier, JF;Vachon, P;Ducharme, MP
通讯作者：
Ducharme, MP
DOI：
10.1042/bj20091857
发表时间：
2010-07-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Calamini B;Ratia K;Malkowski MG;Cuendet M;Pezzuto JM;Santarsiero BD;Mesecar AD
通讯作者：
Mesecar AD
影响因子：
1.8
作者：
De Santi, C;Pietrabissa, A;Pacifici, GM
通讯作者：
Pacifici, GM
影响因子：
1.8
作者：
Lin, Hai-Shu;Yue, Bing-De;Ho, Paul C.
通讯作者：
Ho, Paul C.