Abstract
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.
Footnotes
- Received January 30, 2013.
- Accepted March 8, 2013.
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This work was partially supported by awards from the National Institutes of Health (NIH) National Cancer Institute (NCI) [Grants R03CA133943 and R03CA159389]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NCI.
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This work has been submitted as part of Satish Sharan’s Ph.D. thesis to Temple University.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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