PT  - JOURNAL ARTICLE
AU  - Satish Sharan
AU  - Swati Nagar
TI  - Pulmonary Metabolism of Resveratrol: In Vitro and In Vivo Evidence
AID  - 10.1124/dmd.113.051326
DP  - 2013 May 01
TA  - Drug Metabolism and Disposition
PG  - 1163--1169
VI  - 41
IP  - 5
4099  - http://dmd.aspetjournals.org/content/41/5/1163.short
4100  - http://dmd.aspetjournals.org/content/41/5/1163.full
SO  - Drug Metab Dispos2013 May 01; 41
AB  - 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.