Absorption of sodium γ‐hydroxybutyrate and its Prodrug γ‐butyrolactone: Relationship between in vitro transport and in Vivo absorption

A qualitative relationship between in vitro transport and in vivo absorption of sodium γ‐hydroxybutyrate and γ‐butyrolactone was demonstrated. As with other short‐chain acids, sodium γ‐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.