THE CYP3A4 INHIBITOR ITRACONAZOLE DOES NOT AFFECT THE PHARMACOKINETICS OF A NEW CALCIUM-SENSITIZING DRUG LEVOSIMENDAN

Itraconazole is a potent inbibitor of CYP3A4 isoenzyme and it can caus e clinically significant interactions with some other drugs. Levosimen dan is a new calcium-sensitizing drug intended for congestive heart fa ilure. We aimed to study possible interactions of itraconazole with le vosimendan in healthy volunteers. Twelve healthy male volunteers were included into a randomized, double-blind, two-phase crossover study. A wash-out period of 4 weeks was held between the phases. The subjects were given orally itraconazole 200 mg or placebo daily for 5 days. On the fifth day, they received a single oral dose of 2 mg of levosimenda n. Levosimendan plasma concentrations were determinated up to 12 hours and EGG, heart rate, and blood pressure followed-up to 8 hours after intake of levosimendan. Itraconazole had no significant effects on the pharmacokinetic parameters of levosimendan. Neither were there any di fferences in heart rate, PQ-, QTc- or QRS intervals between the placeb o and itraconazole phases. The systolic blood pressure was decreased s lightly more (p < 0.05) during the itraconazole phase than during the placebo phase. In conclusion, because the potent CYP3A4 inhibitor itra conazole had no significant pharmacokinetic interaction with levosimen dan, interactons with CYP3A4 inhibitor, and oral levosimendan are unli kely.