The Distribution between Plasma and Brain of Glutethimide and 4-Hydroxyglutethimide following Their Administration to Mice

Abstract

Summary

Following administration of d,l-glutethimide or its active metabolite, d-4-hydroxyglutethimide, the presumed d-glutethimide metabolite, to mice, the relative partition between blood and brain as well as the rate of disappearance of each substance from these tissues was found to be similar. In addition, the degree of CNS depression produced by increasing doses of either substance was directly proportional to the blood or brain level attained, indicating that the twofold-greater potency of the active metabolite, relative to glutethimide, is mostly a function of its intrinsic pharmaco-logic activity and not dependent upon differences in drug disposition.