The effect of warfarin on the pharmacokinetics and pharmacodynamics of napsagatran in healthy male volunteers

Faaij, Richard A.; Griensven, J. M. T. Van; Schoemaker, Rik C.; Goggin, Timothy; Guenzi, Alberto; Kroon, Jeffrey; Burggraaf, Jacobus; Cohen, Adam F.

doi:10.1007/s002280100270

Cited by 13 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PiCT determines activities of direct and indirect thrombin inhibitors in a linear manner over a wide concentration range (up to 2,000 ng/ ml) [6]. As PiCT is based on factors affected by oral anticoagulation (FX and FII), this test is presumably also sensitive to oral anticoagulants, just as aPTT and PT are [7][8][9][10], due to lower levels of these factors during therapy with vitamin K antagonists.…”

Section: Introductionmentioning

confidence: 99%

Effect of Phenprocoumon on Monitoring of Lepirudin, Argatroban, Melagatran and Unfractionated Heparin with the PiCT Method

Fenyvesi

Jörg

Harenberg

2002

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melagatran, argatroban and UFH delivered distinct linear additive effects in both plasma sample groups. PiCT ratio reduces differences between both groups with UFH, and argatroban inhibitor-receptor-binding mode plays a role in interaction patterns.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of Phenprocoumon on Monitoring of Lepirudin, Argatroban, Melagatran and Unfractionated Heparin with the PiCT Method

Fenyvesi

Jörg

Harenberg

2002

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

show abstract

“…This is of particular importance for the effects of the combination of the two drugs on the PT at the time the switch from pentasaccharide treatment to oral anticoagulants occurs clinically. In addition, previous studies using a single loading dose of 25 mg of warfarin have been proven to be provide useful information on this relevant issue [5–8].…”

Section: Discussionmentioning

confidence: 99%

Absence of an interaction between the synthetic pentasaccharide fondaparinux and oral warfarin

Faaij

Burggraaf

Schoemaker

et al. 2002

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Aims To investigate the pharmacokinetic and pharmacodynamic interaction of the antithrombotic pentasaccharide fondaparinux (Org31540/SR90107A), given subcutaneously, and oral warfarin in healthy subjects. Methods This study was performed according to a randomised, three-way cross-over, placebo-controlled, double-blind design in 12 healthy male subjects. The treatment consisted of five subcutaneous (s.c.) injections of fondaparinux (4 mg) or placebo at 24 h intervals. Oral dosing of warfarin or placebo was added to the fourth (15 mg) and fifth (10 mg) s.c. injection. Blood samples for pentasaccharide assay, PT and APTT were drawn before the first s.c. dose of the pentasaccharide and over a 6 day period thereafter. Results Fondaparinux administered to healthy male volunteers alone or in combination with oral warfarin was well tolerated and no serious adverse events were observed. No differences were found in the AUC (43 vs 44 mg l − 1 h), C max (645 vs 678 ng ml − 1 ) or elimination half-life (13.8 vs 14.1 h) of fondaparinux between the pentasaccharide-only and the combination treatment. The effect of warfarin on PT (mean maximal increase: 8.2 s.) was not influenced by the presence of the pentasaccharide (mean maximal increase in PT: 9.1 s.). After all treatments a small rise in APTT was seen. No further differences could be detected in the pharmacodynamic parameters following the three treatments. Conclusions The coadministration of warfarin did not influence the pharmacokinetics of fondaparinux in healthy subjects. PT can still be used to monitor the effect of oral anticoagulants during the switch from antithrombotic treatment with pentasaccharide to full oral anticoagulant therapy.

show abstract

“…Remarkable summation effects are reported for prothrombin time [14][15][16] and weaker ones with aPTT [17] or ECT [18][19][20] methods. Controversial data on interference between lepirudin and vitamin K antagonists are reported with the two ECT methods [20,21].…”

Section: Introductionmentioning

confidence: 96%

Comparison of Two Different Ecarin Clotting Time Methods

Fenyvesi

Harenberg

Weiß

et al. 2005

J Thromb Thrombolysis

View full text Add to dashboard Cite

show abstract

The effect of warfarin on the pharmacokinetics and pharmacodynamics of napsagatran in healthy male volunteers

Cited by 13 publications

References 0 publications

Effect of Phenprocoumon on Monitoring of Lepirudin, Argatroban, Melagatran and Unfractionated Heparin with the PiCT Method

Effect of Phenprocoumon on Monitoring of Lepirudin, Argatroban, Melagatran and Unfractionated Heparin with the PiCT Method

Absence of an interaction between the synthetic pentasaccharide fondaparinux and oral warfarin

Comparison of Two Different Ecarin Clotting Time Methods

Contact Info

Product

Resources

About