Studies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol.
Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the treatment of congestive heart failure. In animal experiments levosimendan has potentiated the sedative effects of ethanol. Due to poor water solubility of the compound, ethanol is used as a diluent in the intravenous formulation. In this study the possible interactions between levosimendan and ethanol in human have been studied. Twelve healthy male volunteers were included in this double-blind, randomized, cross-over study. The study consisted of three treatment periods: levosimendan 1 mg intravenously, levosimendan combined with ethanol orally and ethanol 0.8 g/kg alone. Blood samples for determination of levosimendan and ethanol concentrations were collected for 8 h after the dosing. To observe possible pharmacodynamic interactions psychomotoric tests were made before drug administration and 1h, 2h, 3h and 6h thereafter. These tests included Digit symbol substitution test, Maddox wing, Critical Flicker fusion and VAS-test for subjective assessment of performance status. Plasma levosimendan concentrations were not changed by the concomitant ethanol administration. Ethanol did not alter the pharmacokinetics of levosimendan except the volume of distribution of central compartment which was decreased. Levosimendan did neither affect elimination of ethanol. Levosimendan did not potentiate the psychomotoric effects of ethanol neither did it have any psychomotoric effects itself. In conclusion, levosimendan is not likely to have any psychomotoric adverse effects or any clinically significant interactions with ethanol.
Antila
S
S
Orion Pharma, Research Center, Espoo, Finland.
Järvinen
A
A
Akkila
J
J
Honkanen
T
T
Karlsson
M
M
Lehtonen
L
L
D000328:Adult; D019540:Area Under Curve; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005425:Flicker Fusion / Q000187:drug effects; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011724:Pyridazines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077464:Simendan
D002492:Central Nervous System Depressants; D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D000077464:Simendan; D000431:Ethanol