Absorption of sodium gamma-hydroxybutyrate and its prodrug gamma-butyrolactone: relationship between in vitro transport and in vivo absorption.

A qualitative relationship between in vitro transport and in vivo absorption of sodium gamma-hydroxybutyrate and gamma-butyrolactone was demonstrated. As with other short-chain acids, sodium gamma-hydroxybutyrate showed capacity-limited transport in vitro, consistent with the previous observation that this drug exhibited slower in vivo absorption with increasing dose. The prodrug lactone, on the other hand, showed a higher intestinal flux than the acid in the everted gut, and in vivo absorption also was more rapid. Capacity-limited transport and absorption of the lactone appeared less evident. Thus, the increased oral hypnotic activity of the lactone over that of the acid most likely is a result of its more favorable intestinal transport characteristics.