Pharmacology of Levosimendan: A New Myofilament Calcium Sensitizer

Pagel, Paul S.; Haikala, Heimo; Pentikäinen, Pertti J.; Toivonen, M; Nieminen, Markku S.; Lehtonen, Lasse; Jg, Papp; Warltier, David C.

doi:10.1111/j.1527-3466.1996.tb00232.x

Cited by 21 publications

(15 citation statements)

References 63 publications

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“…The concentration inducing 50% of the maximum response for increased contractility (ED50) in isolated guinea-pig papillary muscle is 0.1 M [25]. Data from studies in vitro indicate that the positive inotropic effect of levosimendan in human cardiac tissue is not attenuated by disease, even though there is lot of variability in the inotropic response in the diseased tissue [23].…”

Section: Preclinical Pharmacology Of Levosimendanmentioning

confidence: 94%

“…In addition to the cysteine and cysteinylglycine derivatives mentioned previously, two additional first-pass metabolites have been detected and characterized in human plasma after oral administration [25]. These aminophenylpyridazinone and acetylaminophenylpyridazinone metabolites, designated OR-1855 and OR-1896, respectively, are produced through the activity of intestinal Table 2…”

Section: Clinical Pharmacologymentioning

confidence: 97%

“…In humans, the drug is conjugated to cysteine and cysteinylglycine derivatives [25]. The elimination of total levosimendan, representing both the unchanged drug plus its metabolites, is substantially slower than the elimination of the parent drug [32].…”

Section: Clinical Pharmacologymentioning

confidence: 99%

“…The elimination of total levosimendan, representing both the unchanged drug plus its metabolites, is substantially slower than the elimination of the parent drug [32]. Approximately one third of an intravenous dose is excreted via the urine over 24 hours and a similar proportion to feces over 3 days [25,32]. No alterations in the pharmacokinetics of levosimendan were noted in healthy volunteers, who took levosimendan concomitantly with itraconazole [36].…”

Section: Clinical Pharmacologymentioning

confidence: 99%

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Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure

Lehtonen

2000

Curr Cardiol Rep

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Levosimendan is a new inodilator, whose mechanism of action includes calcium sensitization of contractile proteins and the opening of ATP-dependent potassium channels. The combination of positive inotropy with anti-ischemic effects of K-channel opening offers many potential benefits in comparison to currently available intravenous inotropes, that are more or less contraindicated in patients with ongoing myocardial ischemia. Levosimendan has been extensively studied in various animal models of heart failure, in which the drug has increased contractility without adverse effects on diastolic function. These results have been repeated in patients with heart failure, by whom levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. On higher doses, the drug can induce tachycardia and hypotension. In clinical trials, drug-induced ventricular arrhythmia have been rare. Recently, trials in patients with decompensated heart failure have suggested that short-term intravenous treatment with levosimendan might improve the survival of these critical patients. These results highlight the importance of adequate treatment of the acute heart failure patients for their long-term outcome.

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Section: Preclinical Pharmacology Of Levosimendanmentioning

confidence: 94%

Section: Clinical Pharmacologymentioning

confidence: 97%

Section: Clinical Pharmacologymentioning

confidence: 99%

Section: Clinical Pharmacologymentioning

confidence: 99%

See 2 more Smart Citations

Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure

Lehtonen

2000

Curr Cardiol Rep

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“…The ED 50 (median effective dose) for increased contractility in isolated guinea pig papillary muscle is 0.1 µm [23]. Data from studies in vitro indicate that the positive inotropic effect of levosimendan in human cardiac tissue is not attenuated by disease, even though there is lot of variability in the inotropic response [21].…”

Section: Pharmacology Of Levosimendanmentioning

confidence: 94%

Levosimendan: A calcium-sensitizing agent for the treatment of patients with decompensated heart failure

Lehtonen

2004

Curr Heart Fail Rep

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Levosimendan is a new inodilator. Its mechanism of action includes calcium sensitization of contractile proteins and the opening of adenosine triphosphate-dependent K channels. The combination of positive inotropy with anti-ischemic effects of K-channel opening offers potential benefits in comparison with currently available intravenous inotropes, which are contraindicated in patients with ongoing myocardial ischemia. Levosimendan has been extensively studied in various animal models of heart failure, in which the drug has increased contractility without adverse effects on diastolic function. These results have been repeated in patients with heart failure, in whom levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. The active metabolite of levosimendan (OR-1896) significantly prolongs the duration of the hemodynamic effects of the therapeutic 24-hour levosimendan infusion. Levosimendan has been studied in two major trials with decompensated patients (LIDO and RUSSLAN), in which it showed outcome benefits in comparison with dobutamine and placebo, respectively. A third comparative study (CASINO) recently suggested mortality benefits with levosimendan over placebo and dobutamine. Currently, two large prospective trials (SURVIVE and REVIVE) in patients who are hospitalized because of worsening heart failure are underway. These trials will conclusively prove whether levosimendan should be added to the standard treatment in patients who are hospitalized because of cardiac decompensation.

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Calcium Sensitizer Levosimendan and Its Use in Acute Heart Failure and Related Conditions

Mebazaa

Teerlink

Pollesello

2008

Acute Heart Failure

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Pharmacology of Levosimendan: A New Myofilament Calcium Sensitizer

Cited by 21 publications

References 63 publications

Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure

Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure

Levosimendan: A calcium-sensitizing agent for the treatment of patients with decompensated heart failure

Calcium Sensitizer Levosimendan and Its Use in Acute Heart Failure and Related Conditions

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