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 l evosimendan has potentiated the sedative effects of ethanol. Due to po or water solubility of the compound, ethanol is used as a diluent in t he intravenous formulation. In this study the possible interactions be tween levosimendan and ethanol in human have been studied. Twelve heal thy male volunteers were included in this double-blind, randomized, cr oss-over study. The study consisted of three treatment periods: levosi mendan 1 mg intravenously, levosimendan combined with ethanol orally a nd ethanol 0.8 g/kg alone. Blood samples for determination of levosime ndan and ethanol concentrations were collected for 8 h after the dosin g. To observe possible pharmacodynamic interactions psychomotoric test s were made before drug administration and 1h, 2h, 3h and 6h thereafte r. These tests included Digit symbol substitution test, Maddox wing, C ritical Flicker fusion and VAS-test for subjective assessment of perfo rmance status. Plasma levosimendan concentrations were not changed by the concomitant ethanol administration. Ethanol did not alter the phar macokinetics of levosimendan except the volume of distribution of cent ral compartment which was decreased. Levosimendan did neither affect e limination of ethanol. Levosimendan did not potentiate the psychomotor ic effects of ethanol neither did it have any psychomotoric effects it self. In conclusion, levosimendan is not likely to have any psychomoto ric adverse effects or any clinically significant interactions with et hanol.