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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The CYP3A4 inhibitor intraconazole does not affect the pharmacokinetics of a new calcium-sensitizing drug levosimendan.

Itraconazole is a potent inhibitor of CYP3A4 isoenzyme and it can cause clinically significant interactions with some other drugs. Levosimendan is a new calcium-sensitizing drug intended for congestive heart failure. We aimed to study possible interactions of itraconazole with levosimendan 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 levosimendan. Levosimendan plasma concentrations were determined up to 12 hours and ECG, 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 differences in heart rate, PQ-, QTc- or QRS intervals between the placebo and itraconazole phases. The systolic blood pressure was decreased slightly more (p < 0.05) during the itraconazole phase than during the placebo phase. In conclusion, because the potent CYP3A4 inhibitor itraconazole had no significant pharmacokinetic interaction with levosimendan, interactions with CYP3A4 inhibitor, and oral levosimendan are unlikely.[1]


  1. The CYP3A4 inhibitor intraconazole does not affect the pharmacokinetics of a new calcium-sensitizing drug levosimendan. Antila, S., Honkanen, T., Lehtonen, L., Neuvonen, P.J. International journal of clinical pharmacology and therapeutics. (1998) [Pubmed]
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