Cardiovascular effects and plasma level profile of pimobendan (UD-CG 115 BS) and its metabolite UD-CG 212 in patients with congestive heart failure after single and repeated oral dosing.
Pimobendan (10 mg on day 1, then 5 mg twice daily for 28 days) was administered orally to nine patients in class III-IV stable congestive heart failure. On day 1, pimobendan appeared in plasma within 30 min, its plasma concentration peaked at 39 +/- 23 ng/ml after 1.5 h, and then decreased with a half-life of 1.44 +/- 0.94 h. Concentrations of its major metabolite UD-CG 212 peaked 3 h after drug intake, at 24 +/- 7 ng/ml. The time course of plasma concentrations was similar on days 1, 2, and 28. Cardiac index increased from 2.2 +/- 0.5 to 2.8 +/- 0.4 L.min-1.m-2 (p = 0.0001) on day 1, from 2.8 +/- 0.5 to 3.4 +/- 0.4 L.min-1.m-2 (p = 0.0032) on day 2, and stayed at 2.7 +/- 0.6 and 2.7 +/- 0.9 L.min-1.m-2 (p = 0.7895) on day 28. On day 1, pulmonary capillary wedge pressure decreased from 16 +/- 7 to 6 +/- 5 mm Hg (p = 0.0001), from 10 +/- 7 to 7 +/- 8 mm Hg (p = 0.0001) on day 2, and from 9 +/- 7 to 5 +/- 3 mm Hg (p = 0.0275) on day 28. Cardiovascular effects of pimobendan were independent of plasma concentrations. All patients improved by at least one NYHA functional class; exercise tolerance increased. No side effect was observed, but two patients died suddenly: Arrhythmogenicity should be ruled out before pimobendan is recommended for treatment of heart failure.
Hagemeijer
F
F
Department of Cardiology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
Brand
H J
HJ
Roth
W
W
D000368:Aged; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005080:Exercise Test; D005260:Female; D005951:Glucose Tolerance Test; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D013997:Time Factors
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; C047936:UD CG 212 Cl