Kinetics of the enantiomers of vigabatrin after an oral dose of the racemate or the active S-enantiomer

Clin Pharmacol Ther. 1986 Nov;40(5):581-6. doi: 10.1038/clpt.1986.227.

Abstract

Six healthy men received single oral doses of 1500 mg of vigabatrin [(R,S)-gamma-vinyl-GABA] and 750 mg of S(+)-gamma-vinyl-GABA on two occasions. Concentrations of the individual enantiomers were assayed by a stereoselective procedure based on combined GC/MS. At peak, concentrations of the R(-)-enantiomer exceeded concentrations of the S(+)-enantiomer, with an approximate ratio of 2:1. The mean terminal t1/2 ranged from 6 to 8 hours for both enantiomers. Mean urinary recovery of the S(+)-enantiomer was 49% after both doses and was 65% for the R(-)-enantiomer. Plasma concentration values obtained for the S(+)-enantiomer after a dose of the pure S(+)-enantiomer and an equivalent dose of the racemate showed good agreement for both the concentrations observed at any time point and the elimination characteristics, demonstrating bioequivalence. Renal clearance values for the S(+)-enantiomer are not affected by concomitant dosing with the pharmacologically inactive R(-)-enantiomer. No chiral inversion was detected after dosing with the pure S(+)-enantiomer.

MeSH terms

  • 4-Aminobutyrate Transaminase / antagonists & inhibitors*
  • Administration, Oral
  • Adult
  • Aminocaproates / administration & dosage
  • Aminocaproates / metabolism*
  • Biological Availability
  • Humans
  • Kinetics
  • Male
  • Stereoisomerism
  • Vigabatrin

Substances

  • Aminocaproates
  • 4-Aminobutyrate Transaminase
  • Vigabatrin