Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA.
Drug Metab Dispos. 2013 May;41(5):1163-9. doi: 10.1124/dmd.113.051326. Epub 2013 Mar 8.
The role of pulmonary metabolism in trans-resveratrol (RES) pharmacokinetics was studied in a mouse model. Plasma concentrations of RES and its major metabolites trans-resveratrol-3-sulfate (R3S) and trans-resveratrol-3-glucuronide (R3G) were compared after administration of RES by intravenous (IV) and intra-arterial (IA) routes. Total area under the curve (AUC) of RES decreased by approximately 50% when RES was administered by the IV route compared with the IA route. The AUC of R3G was also significantly higher in mice administered RES by the IV route compared with the IA route. In vitro studies performed with mouse and human lung fractions confirmed pulmonary metabolism of RES. Interestingly, mouse-lung fractions gave rise to both R3S and R3G, whereas human lung fractions yielded R3S. This indicates marked interspecies variation in RES conjugation, especially in the context of extrapolating rodent data to humans. Taken together, the results presented here underline, for the first time, the impact of pulmonary metabolism on resveratrol pharmacokinetics and interspecies differences in RES pulmonary metabolism.
在小鼠模型中研究了肺代谢在反式白藜芦醇（RES）药代动力学中的作用。静脉（IV）和动脉内（IA）给予 RES 后，比较了 RES 及其主要代谢物反式白藜芦醇-3-硫酸盐（R3S）和反式白藜芦醇-3-葡萄糖醛酸苷（R3G）的血浆浓度。与 IA 途径相比，通过 IV 途径给予 RES 时，RES 的总曲线下面积（AUC）降低了约 50%。与 IA 途径相比，通过 IV 途径给予 RES 的小鼠中 R3G 的 AUC 也显着更高。用小鼠和人肺部分进行的体外研究证实了 RES 的肺代谢。有趣的是，小鼠肺部分产生了 R3S 和 R3G，而人肺部分产生了 R3S。这表明 RES 结合在种间存在显着差异，特别是在将啮齿动物数据外推到人类的情况下。总之，这里提出的结果首次强调了肺代谢对 RES 药代动力学的影响以及 RES 肺代谢在种间的差异。
