Comparison of the pharmacokinetics of intravenously administered rac-baclofen and its (-) - (R) - and (+) - (S) -enantiomers in dogs
Wuis, E.W.; Dirks, M.J.; Termond, E.F.; Vree, T.B.; Van der Kleijn, E.
International Journal of Clinical Pharmacology Research 9(4): 239-246
1989
ISSN/ISBN: 0251-1649 PMID: 2777427 Document Number: 333605
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.