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Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin.

Abstract：

OBJECTIVE:To study the effects of possible interactions between levosimendan and warfarin on pharmacokinetics and pharmacodynamics. Furthermore, the effects of levosimendan on blood coagulation were investigated. METHODS:Open, randomised cross-over design with two treatment phases was used. During one phase, levosimendan (0.5 mg four times daily) was given orally to ten healthy subjects for 9 days. On the fourth treatment day with levosimendan, a single oral dose of warfarin (25 mg) was given. Pharmacokinetic parameters of levosimendan from the third and fourth treatment days were compared with each other. During the other treatment phase the subjects received only a single dose of warfarin. Pharmacokinetic parameters of warfarin alone were compared with those determined after concomitant administration of levosimendan. Changes in blood coagulation parameters were evaluated after levosimendan and warfarin alone and after concomitant administration. RESULTS:Warfarin did not change the pharmacokinetics of levosimendan. The distribution volume of warfarin was higher and elimination half-life shorter after concomitant levosimendan administration than after warfarin alone. However, concomitant levosimendan administration did not potentiate the effects of warfarin on blood coagulation assessed using activated partial thromboplastin time (APTT) and thromboplastin time (TT-SPA). Levosimendan alone for 3 days did not change APTT or TT-SPA values. There were no changes in the protein binding of levosimendan or warfarin upon concomitant administration. Continuous treatment with oral levosimendan caused headache, which was probably due to cerebral vasodilation. CONCLUSIONS:Concomitant levosimendan administration did not potentiate the effect of warfarin on blood coagulation after a single dose. Levosimendan itself had no effects on blood coagulation.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Antila S,Jarvinen A,Honkanen T,Lehtonen L

doi

10.1007/s002280000204

subject

Has Abstract

pub_date

2000-12-01 00:00:00

pages

705-10

issue

9-10

eissn

0031-6970

issn

1432-1041

journal_volume

pub_type

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Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin.