Improved pharmacological activity via pro-drug modification: comparative pharmacokinetics of sodium gamma-hydroxybutyrate and gamma-butyrolactone.

摘要: Although gamma-butyrolactone (GBL) rapidly converts to gamma-hydroxybutyrate (GHB) in vivo, the lactone gave significantly more prolonged hypnotic effects than GHB when equimolar doses were compared both parenterally and orally rats. Plasma drug concentrations higher after GBL administration through routes, consistent with observed differences pharmacological activity of these two compounds. Oral was absorbed much faster oral GHB, dual decreasing potential first-pass metabolism elevating plasma region where capacity-limited elimination is operative. Parenteral produced a slower initial clearance parenteral GHB. In spite rapid apparent tissue distribution compounds may be different.