title: Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin.
abstract: This study evaluated the potential impact of concomitant digoxin on the pharmacokinetics and pharmacodynamics of dabigatran etexilate, a novel oral direct thrombin inhibitor. Healthy volunteers (n = 23) received 150 mg dabigatran etexilate twice daily on days 1 to 3 and once on day 4 in 1 period. Digoxin was given in another period as a loading dose of 0.5 mg early on day 1 and 0.25 mg in the evening of day 1 and on the mornings of days 2 to 4. In a third treatment period, dabigatran etexilate together with digoxin was given on days 1 to 4. Exposure to dabigatran was not significantly altered with concomitant digoxin-the maximum concentration (Cmax,ss ) and area under the concentration-time curve at steady state over 1 dosing interval (AUCτ,ss ) of dabigatran with and without digoxin were essentially unchanged. The pharmacokinetic profile of digoxin also remained unchanged in the presence of dabigatran etexilate. Dabigatran's anticoagulant effect, assessed by blood coagulation time assays, was not influenced by digoxin. Dabigatran etexilate and digoxin can be coadministered without the need for dose adjustment of either drug.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, GermanyMedical Data Services, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, GermanyClinical Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, GermanyClinical Pharmacology Research, PAREXEL International GmbH, Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Stangier
authors.forename: Hildegard
authors.initials: H
authors.lastname: Stähle
authors.forename: Karin
authors.initials: K
authors.lastname: Rathgen
authors.forename: Willy
authors.initials: W
authors.lastname: Roth
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reseski
authors.forename: Thomas
authors.initials: T
authors.lastname: Körnicke
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000991:Antithrombins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D001777:Blood Coagulation / Q000187:drug effects; D018592:Cross-Over Studies; D000069604:Dabigatran; D004077:Digoxin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D000991:Antithrombins; D001562:Benzimidazoles; D011725:Pyridines; D004077:Digoxin; D000069604:Dabigatran