Pharmacokinetics and pharmacodynamics of enantiomers of pimobendan in patients with dilated cardiomyopathy and congestive heart failure after single and repeated oral dosing

Kai Min Chu, Shyh Ming Shieh, Oliver Yoa Pu Hu

研究成果: 雜誌貢獻文章同行評審

26 引文 斯高帕斯(Scopus)

摘要

Pharmacokinetics and pharmacodynamics of pimobendan were studied in eight patients with dilated cardiomyopathy and chronic congestive heart failure after single dosing and after 2-week repeated dosing of 5 mg racemic pimobendan. Enantiomers of pimobendan and its demethylated metabolite in plasma and in red blood cells were measured. In the single-dose study, the peak plasma levels of 16.3 ± 4.0 and 17.0 ± 3.1 ng/ml of (+)- and (-)-pimobendan were observed at 0.9 hour after dosing. The concentration-time curves followed a two-compartment model, with terminal half-lives of 2.56 ± 0.35 and 2.93 ± 0.33 hours for (+)- and (-)-pimobendan (p > 0.05), respectively. The oral volumes of distribution after equilibrium were 3.26 ± 0.74 and 3.13 ± 0.75 L/kg, and oral clearances were 28.6 ± 7.0 and 21.9 ± 4.1 ml/min/kg for (+)- and (-)-pimobendan (p > 0.05), respectively. In red blood cells, the respective (+)- and (-)-pimobendan concentrations were 5.8 and 8.4 times higher than those in plasma, indicating a stereoselective partitioning of drugs between plasma and red blood cells. The pharmacodynamic effect of pimobendan was evaluated by echocardiography. The ejection fraction, mean velocity of circumferential fiber shortening, aortic flow peak velocity, cardiac index, and stroke volume index significantly increased 50% to 60%. The left ventricular end-systolic dimension, systolic blood pressure, and diastolic blood pressure significantly decreased 8% to 11%. These effects lasted for more than 8 hours. In a 2-week repeated-dose study, there was no significant dose accumulation in plasma and red blood cells. The pharmacokinetic parameters were similar to those in the single-dose study, except for significantly shorter absorption half-lives. The baseline levels of cardiac index and stroke volume index were significantly higher than the baseline levels in the single-dose study. This suggests an accumulation of pharmacodynamic effects despite a relatively short elimination half-life.
原文英語
頁(從 - 到)610-621
頁數12
期刊Clinical Pharmacology and Therapeutics
57
發行號6
DOIs
出版狀態已發佈 - 一月 1 1995
對外發佈Yes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

指紋 深入研究「Pharmacokinetics and pharmacodynamics of enantiomers of pimobendan in patients with dilated cardiomyopathy and congestive heart failure after single and repeated oral dosing」主題。共同形成了獨特的指紋。

引用此