Comparison of the pharmacokinetics of intravenously administered rac-baclofen and its (-)-(R)- and (+)-(S)-enantiomers in dogs.
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.
Wuis
E W
EW
Department of Clinical Pharmacy, St. Radboud University Hospital, Nijmegen, The Netherlands.
Dirks
M J
MJ
Termond
E F
EF
Vree
T B
TB
Van der Kleijn
E
E
D000818:Animals; D001418:Baclofen / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004285:Dogs; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D013237:Stereoisomerism
D001418:Baclofen