COMPARISON OF THE PHARMACOKINETICS OF INTRAVENOUSLY ADMINISTERED RAC-BACLOFEN AND ITS (-)-(R)-ENANTIOMERS AND (+)-(S)-ENANTIOMERS IN DOGS

  • 1 January 1989
    • journal article
    • research article
    • Vol. 9  (4) , 239-246
Abstract
Baclofen is a centrally acting muscle relaxant marketed as the racemate. Since only the (-)-(R)-enantiomer is pharmacologically active, the pharmacokinetics of rac-baclofen and its enantiomers were studied individually in the same group of dogs to determine if there was any stereospecificity in the drug''s kinetics after a single intravenous dose. High-pressure liquid chromatography was used to determine concentrations in plasma and urine. A major difference was found in the urinary recovery of the unchanged drug. Only about 50% of the dose of the clinically used racemate appeared as unchanged drug in the urine; whereas the active (-)(R)-isomer was for the most part renally excreted (85%). irrespective of isomeric composition, the renal clearance was dependent upon the creatinine clearance. Differences in non-renal clearance could not be explained by stereoselective formation of the .gamma.-hydroxymetabolite. It is concluded that in the dog, the active enantiomer is also pharmacokinetically preferred.

This publication has 0 references indexed in Scilit: