Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers.
Potential pharmacokinetic and pharmacodynamic interactions between a new low molecular weight heparinoid Org 10172 (bolus injection of 3250 anti-Xa units) and digoxin (0.25 mg once daily for 8 days) were studied in 6 healthy male volunteers using an open, randomised three-way cross-over design. Digoxin produced a slight increase in clearance of anti-Xa activity from 4.3 to 4.8 ml.min-1, while plasma antithrombin and thrombin generation inhibiting (TG1) activity remained unchanged. Digoxin did not affect the actions of Org 10172 on the clotting tests. In the presence of Org 10172 there was a reduction in the AUC of digoxin during one dosing interval after the seventh digoxin tablet from 20 to 17 ng.ml-1.h, and a significant reduction in the average serum digoxin concentration. Since renal digoxin clearance was not significantly changed this probably might be due to a change in the non-renal clearance of digoxin. Atrio-ventricular node conduction, as measured by PR-time intervals, remained unchanged during all three treatments. In conclusion, although the pharmacokinetics of Org 10172 and digoxin were slightly changed by the combination, it is probably safe to administer Org 10172 and digoxin simultaneously. The clinical relevance of the slight decrease in plasma anti-Xa activity levels cannot yet be defined.
de Boer
A
A
Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
Stiekema
J C
JC
Danhof
M
M
Moolenaar
A J
AJ
Breimer
D D
DD
D000284:Administration, Oral; D000328:Adult; D001283:Atrioventricular Node / Q000187:drug effects; D001780:Blood Coagulation Tests; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006497:Heparan Sulfate; D006801:Humans; D007275:Injections, Intravenous; D008297:Male
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004077:Digoxin; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; C035838:danaparoid