W/O and O/W emulsions of tegafur(50mg/5ml/kg) were oraly administered to rats to compare with their mesenteric lymphatic delivery effects. And also in order to demonstrate the lymph targeting associated to the oral route, it was deemed necessary
to
investigate the fate of solution after oral administration as a control. Lymph and plasma samples were periodically take from each subject of mesenteric lymphatic duct cannulated rats. Then, lymph and plasma levels of tegafur and its active
metabolite,
5-FU, were simultaneously observed. Also pharmacokinetic parameters were compared with each others. On the other, hand, most previous studies of lymphatic transport have not addressed the question of whether an increase in mesenteric or thoracic
lymph
transport by the manipulation of a suspected variable was due to selective delivery to the intestinal lymphatics or an overall increased availability. Therefore, lymphatic on a physiologically based pharmacokinetic model which represents the
characteistics of lymphatic systems, we are also going to determine the contributions of mesenteric lymph transport versus thoracic lymph transport of tegafur reported in reported in reference(13). Ion comparison with tegafur solution. AUS and
mean
residence time of plasma tegafur were significantly increased in W/O emulsion but significantly decreased emulsion. AUC of tegafur in mesenteric lymph and in plasma for W/O emulsion were 3.7 times and 2.9 times more than those for O/W emulsion,
respectively. And AUC of 5-FU in thoracic lymph for W.O emulsion was 3.7 times more than that for O/W emulsion. These results suggested that lymphatic delivery of tegafur by W/O emulsion was more effective than that by O/W emulsion due to its
differences of formation ability of chylomicrons.
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