Pharmacokinetics and metabolism of bisoprolol enantiomers in humans

J Pharm Sci. 1998 Mar;87(3):289-94. doi: 10.1021/js970316d.


The plasma concentrations and urinary excretions of bisoprolol enantiomers in four Japanese male healthy volunteers after a single oral administration of 20 mg of racemic bisoprolol were evaluated. The AUC(infinity) and elimination half-life of (S)-(-)-bisoprolol were slightly larger than those of (R)-(+)-bisoprolol in all subjects. The metabolic clearance of (R)-(+)-bisoprolol was significantly (P < 0.05) larger than that of (S)-(-)-bisoprolol (S/R ratio: 0.79+/-0.03), although the difference was small. In contrast, no stereoselective in vitro protein binding of bisoprolol in human plasma was found. An in vitro metabolic study using recombinant human cytochrome P450 (CYP) isoforms indicated that oxidation of both bisoprolol enantiomers was catalyzed by the two isoforms, CYP2D6 and CYP3A4. CYP2D6 metabolized bisoprolol stereoselectively (R > S), whereas the metabolism of bisoprolol by CYP3A4 was not stereoselective. The S/R ratio of the mean clearance due to renal tubular secretion was 0.68, indicating a moderate degree of stereoselective renal tubular secretion. These findings taken together suggest that the small differences in the pharmacokinetics between (S)-(-)- and (R)-(+)-bisoprolol are mainly due to the stereoselectivity in the intrinsic metabolic clearance by CYP2D6 and renal tubular secretion.

Publication types

  • Clinical Trial

MeSH terms

  • Adrenergic beta-Antagonists / blood
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Adrenergic beta-Antagonists / urine
  • Area Under Curve
  • Bisoprolol / blood
  • Bisoprolol / pharmacokinetics*
  • Bisoprolol / urine
  • Blood Proteins / metabolism
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Half-Life
  • Humans
  • Male
  • Mixed Function Oxygenases / metabolism
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Reference Values
  • Stereoisomerism


  • Adrenergic beta-Antagonists
  • Blood Proteins
  • Recombinant Proteins
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Bisoprolol