Biochemical Study for Absorption Mechanism of Lipophilic Drug from Intestine to Lymphatic fluid

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Ubidecarenone was employed as a model drug for lipophilic drugs. After drug was administered into the stomach of rats, lymphatic fluid and portal vein blood were collected and subjected to HPLC analysis for drug quantification. Ubidecarenone was found to transfered selectively to lymphatic fluid. When glycerol mono-olate was co-administerd to rats, lymphatic absorption was increased about 3-fold. The absorption of ubidecarenone to lymphatic fluid was suppressed by monensine, endocytosis inhibitor, and it also inhibited the binding of ubidecarenone to intestinal tissue in vitro. Both the facts suggest that endocytosis plays an important role for lymphatic absorption of ubidecarenone. Moreover, 85% of ubidecarenone was found to be in the reduced-form in lymphatic fluid even when the oxidized-form of ubidecarenone was administered. This phenomenon is very precious and important and should be pursued further. Ubidecarenone was found to be reduced by enzyme during the absorption phase and not in the intestine nor in the lymphatic fluid. Enzyme, which is located in the plasma membrane, responsible for this reduction is sensitive against sulfydryl inhibitors.These results imply that the role of ubidecarenone reduction in the lymphatic absorption throught endocytosis should be studied intensively.