Kinetics and metabolism of (+)-, (-)- and (+/-)-bufuralol

Eur J Clin Pharmacol. 1982;23(6):529-33. doi: 10.1007/BF00637501.

Abstract

Single oral doses of (+)-, (-)- and (+/-)-bufuralol were administered to a healthy volunteer to compare the disposition and metabolism of the individual isomers and the racemate. Plasma levels and area under plasma curve (AUC) of the active isomer, (-)-bufuralol, were higher than those of the (+)-isomer; plasma clearance was correspondingly lower. Intermediate values were found for the racemate. The elimination half-life of (-)-bufuralol was shorter than that of (+)-bufuralol, but similar to the racemate. Both isomers were cleared almost entirely by metabolism. The main metabolic pathway for (-)-bufuralol was aromatic hydroxylation, whereas the principal route for (+)-bufuralol was conjugation. Phenol metabolites in the systemic circulation were present mainly as conjugates. Both isomers also underwent aliphatic hydroxylation. This pathway was more favoured by the (+)-isomer, although plasma levels and AUC of the principal product, 2'-hydroxy-bufuralol, were almost identical for the two forms. Major differences in metabolic fate thus had relatively little effect on the disposition of pharmacologically active metabolites.

MeSH terms

  • Adrenergic beta-Antagonists / blood
  • Adrenergic beta-Antagonists / metabolism*
  • Adrenergic beta-Antagonists / urine
  • Adult
  • Ethanolamines / blood
  • Ethanolamines / metabolism*
  • Ethanolamines / urine
  • Humans
  • Kinetics
  • Male

Substances

  • Adrenergic beta-Antagonists
  • Ethanolamines
  • bufuralol