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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.

Abstract
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.
AuthorsF Hagemeijer, W Roth, H J Brand
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 14 Suppl 2 Pg. S57-64 ( 1989) ISSN: 0160-2446 [Print] United States
PMID2478794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cardiotonic Agents
  • Pyridazines
  • pimobendan
  • UD CG 212 Cl
Topics
  • Administration, Oral
  • Aged
  • Cardiotonic Agents (adverse effects, blood, pharmacology)
  • Cardiovascular System (drug effects)
  • Female
  • Heart Failure (blood)
  • Hemodynamics (drug effects)
  • Humans
  • Male
  • Middle Aged
  • Pyridazines (adverse effects, blood, pharmacology)
  • Time Factors

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