Pharmacokinetic profile epilutein, lutein and zeaxanthin following intravenous and oral administration in rats

The aim of these investigations was to assess the role of 3'-epilutein (3) in the overall xanthophyll supply in rats. Three studies with (3R,3‘R,6‘R)-lutein (1), (3R,3‘R)-zeaxanthin (2) or 3'-epilutein (3) treatments were performed in groups of 7-10 week old Sprague-Dawley rats. In the first, the animals received two single intravenous (i.v.) doses separated by a wash-out period of 14 days. (3R,3‘R,6‘R)-lutein (1) and (3R,3‘R)-zeaxanthin (2) were administered at comparably high dose levels without (period 1) or together with (period 2) high dose 3'-epilutein (3). The second protocol was similar to the first but with substantial lower dose levels. In the third, low doses of lutein were administered orally for seven consecutive days (period 1) followed by equally low doses of (3R,3‘R,6‘R)-lutein (1) and 3'-epilutein (3) (period 2). Plasma levels were determined at different time periods and the pharmacokinetic parameters were calculated. The AUC_0-t for (3R,3‘R)-zeaxanthin (2) was increased by almost 40% in presence of co-administered 3'-epilutein (3). 3'-Epilutein (3) was observed in all plasma samples of rats receiving (3R,3‘R,6‘R)-lutein (1), and (3R,3‘R)-zeaxanthin (2). The 3'-oxolutein (4) concentrations observed in rats treated with 3'-epilutein (3) were lower when compared to the treatment without 3'-epilutein (3). These effects were found to be dose proportional. In the protocol with oral administration the dosecorrected C_max and AUC_0-24h of (3R,3‘R,6‘R)-lutein (1) appeared to be doubled in presence of 3'-epilutein (3). At the same time the C_max and AUC_0-24h of 3'-epilutein (3) were about 50% lower than obtained for (3R,3‘R,6‘R)-lutein (1) administered at the same dose.