Correlations between the cardiovascular effects of pimobendan and plasma concentrations of the parent compound and of its major active metabolite, UD-CG 212 CL, in patients with congestive heart failure.
Pimobendan was administered orally (10 mg single dose on day 1, then 5 mg twice daily for 4 weeks) to nine patients with chronic heart failure undergoing hemodynamic monitoring. The time course of changes in plasma concentrations of pimobendan and of its major active metabolite. UD-CG 212 CL, was similar on days 1, 2, and 28. Pimobendan plasma levels peaked 1.5-2.0 h after drug intake: plasma concentrations of UD-CG 212 CL reached a maximum 1 h later; the terminal half-life of pimobendan in plasma varied between 1.44 +/- 0.94 h on day 1 and 1.19 +/- 0.36 h on day 2. Initially, cardiovascular variables changed with increasing plasma drug levels and reached a maximum 4 h after pimobendan intake; later, we found no correlation between plasma concentrations and hemodynamic effects. A steady state of hemodynamic improvement was achieved after 4 weeks of maintenance therapy with pimobendan. Baseline pulmonary capillary wedge pressure dropped from 16 +/- 7 mm Hg on day 1 to 5 +/- 3 mm Hg at noon on day 28 (-69%; p less than 0.001), and baseline cardiac index increased from 2.2 +/- 0.5 L/min/m2 on day 1 to 2.7 +/- 0.9 L/min/m2 on day 28 (+23%; p less than 0.01). Pimobendan is a long-acting drug that effectively improves cardiac performance in patients with chronic congestive heart failure.
Hagemeijer
F
F
Department of Cardiology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
Roth
W
W
Brand
H J
HJ
D000284:Administration, Oral; D000368:Aged; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D013997:Time Factors
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; C047936:UD CG 212 Cl