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 -t -kg-1; 1.74 1 โข kg -1 and 2.34 1. 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 1.2h, were 15.8 and 16.8 ng-m1-1, 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 1. kg-1.) Similar phenomena were found after IV administration.