caa a22 4500 475819330 CHVBK 20180406123818.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1007/s002280000204 doi (NATIONALLICENCE)springer-10.1007/s002280000204 Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin [Elektronische Daten] [Saila Antila, Asko Jarvinen, Timo Honkanen, Lasse Lehtonen] 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 (0.5mg four times daily) was given orally to ten healthy subjects for 9days. On the fourth treatment day with levosimendan, a single oral dose of warfarin (25mg) 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 3days 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. Springer-Verlag, 2000 Levosimendan Pharmacokinetics Calcium sensitisers nationallicence Antila Saila Orion Pharma, Research Centre, P.O. Box 65, FIN-02101 Espoo, Finland aut Jarvinen Asko Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland aut Honkanen Timo Deaconess Hospital, Alppikatu 2, FIN-00530 Helsinki, Finland aut Lehtonen Lasse Orion Pharma, Research Centre, P.O. Box 65, FIN-02101 Espoo, Finland aut European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 705-710 0031-6970 56:9-10<705 2000 56 228 https://doi.org/10.1007/s002280000204 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000204 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Antila Saila Orion Pharma, Research Centre, P.O. Box 65, FIN-02101 Espoo, Finland aut NATIONALLICENCE 700 1- Jarvinen Asko Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland aut NATIONALLICENCE 700 1- Honkanen Timo Deaconess Hospital, Alppikatu 2, FIN-00530 Helsinki, Finland aut NATIONALLICENCE 700 1- Lehtonen Lasse Orion Pharma, Research Centre, P.O. Box 65, FIN-02101 Espoo, Finland aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 705-710 0031-6970 56:9-10<705 2000 56 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer