Plasma and red blood cell pharmacokinetics of pimobendan enantiomers in healthy Chinese

Eur J Clin Pharmacol. 1995;47(6):537-42. doi: 10.1007/BF00193708.

Abstract

The pharmacokinetics of enantiomers of pimobendan and their demethylated metabolites in plasma and red cells were studied in 8 normal healthy volunteers. After racemic pimobendan 5 mg IV, the plasma concentration-time curve followed a two-compartment open-model with elimination half-lives of 1.81 h and 1.86 h for (+)- and (-)-pimobendan, respectively. The clearances and volumes of distribution postequilibrium were 13.5 ml.min-1.kg-1, 14.4 ml.min-1.kg-1; 1.74 l.kg-1 and 2.34 l.kg-1 for (+)- and (-)-pimobendan, respectively. Plasma protein binding (n = 3) of (+)-, (-)-pimobendan, (+)- and (-)-demethylated metabolites was 97.6, 97.6, 92.2 and 92.5%, respectively. The plasma concentration-time curve also followed a two-compartment open model after oral administration of 7.5 mg racemic pimobendan. The absolute bioavailabilities of (+)- and (-)-pimobendan were 0.51 and 0.55. Peak levels of (+)- and (-)-pimobendan, both at 1.2 h, were 15.8 and 16.8 ng.ml-1, respectively. The (+)- and (-)-pimobendan concentrations in red cells were determined and their pharmacokinetics were estimated using red blood cell data. Interesting phenomena were observed: the peak concentrations of (+)- and (-)-pimobendan in red blood cells were about 5.5- and 9.2-times higher than in plasma, and the AUCs were correspondingly elevated. The volume of distribution of the central compartment of (-)-pimobendan in red cell was significantly smaller than that of (+)-pimobendan. (0.24 vs. 0.42 l.kg-1.) Similar phenomena were found after IV administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiotonic Agents / pharmacokinetics*
  • Erythrocytes / metabolism*
  • Humans
  • Male
  • Protein Binding
  • Pyridazines / pharmacokinetics*
  • Stereoisomerism
  • Vasodilator Agents / pharmacokinetics*

Substances

  • Cardiotonic Agents
  • Pyridazines
  • Vasodilator Agents
  • pimobendan