@article {Garrigou-Gadenne574, author = {D Garrigou-Gadenne and A Durand and J P Thenot and P L Morselli}, title = {The disposition and pharmacokinetics of alpidem, a new anxiolytic, in the rat.}, volume = {19}, number = {3}, pages = {574--579}, year = {1991}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The autoradiographic distribution, disposition, biliary excretion, and pharmacokinetics of alpidem in Sprague-Dawley rats were evaluated after iv or oral administration. Following i.v. administration, autoradiography showed that radioactivity was preferentially localized in lipid-rich tissues including central nervous system structures. After a 3-mg.kg-1 i.v. or oral dose of [14C]alpidem, more than 80\% of the radioactivity were excreted in the feces over a 6-day period. Biliary excretion of radioactivity in vigile rats, about 74\% of the dose over a 7-hr period after either iv or oral administration, showed that alpidem was well absorbed. The absolute bioavailability (13\%) data indicated a high first-pass effect. Plasma pharmacokinetic parameters of alpidem were as follows: Vd = 5 liter.kg-1, Cl = 2.2 liter.h-1.kg-1, and terminal t 1/2 beta = 1.2-1.7 hr. Three metabolites with a pharmacological activity similar to that of alpidem were detected in plasma. They were eliminated from the central compartment with half-lives comparable to that of the parent drug. Alpidem crossed the blood-brain barrier following either i.v. or oral administration, resulting in cerebral levels 2.5 to 4 times greater than the plasma levels. Alpidem was eliminated from the central nervous system according a biphasic process with a t 1/2 alpha comparable in plasma and brain. Alpidem represented 94 and 63\% of cerebral radioactivity 5 min after i.v. and oral administration, respectively. Two out of the three active plasma metabolites were detected in the brain.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/19/3/574}, eprint = {https://dmd.aspetjournals.org/content/19/3/574.full.pdf}, journal = {Drug Metabolism and Disposition} }