Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin
Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin
Dabigatran (Pradaxa ®) is a new oral anticoagulant. It is used to prevent venous
 thromboembolism in orthopedic surgery and has recently demonstrated efficacy and safety at
 least as good as anticoagulants in the prevention of thromboembolism in atrial fibrillation
 and the treatment of venous thromboembolism. It is administered with fixed dose and does not
 require laboratory monitoring because of the low inter and intra individual pharmacokinetic
 (PK) and pharmacodynamics (PD) of dabigatran. However, the bioavailability of dabigatran is
 very low (6.5%) and is controlled by an efflux protein, P-GP. This molecule has a genetic
 polymorphism. The inhibition of this protein can cause a significant increase in intestinal
 absorption of dabigatran and expose patients to a risk of bleeding by overdose. Two major
 drug interactions have been identified : quinidine (cons-indication) and amiodarone
 (precautions). It is likely that other interactions exist and can be clinically significant
 in patients not selected such as testing. The development of tools to study the influence of
 P-GP on the PK and PD of dabigatran is therefore interesting. As the P-GP has a genetic
 polymorphism, the study of the latter is an important element in the detection of drug
 interactions. In this sense, clarithromycin, a potent inhibitor of P-GP is a good model to
 evaluate the primary mechanism of drug interaction of dabigatran and optimize the
 experimental design of studies to be conducted.
Inclusion Criteria:

 -  affiliated or beneficiary of a social security category

 -  having signed the inform consent form

 -  having signed the genetic consent form

 -  weight between 60 and 85 kg

 -  normal clinical exam

 -  normal biological exam

 Exclusion Criteria:

 -  contra-indication to dabigatran

 -  contra-indication to clarithromycin

 -  previous history of psychiatric disease, or antidepressant treatment, or convulsion,
 or hemorrhagic disease

 -  smoker

 -  peptic ulcer

 -  severe liver disease

 -  severe kidney failure

 -  previous surgery within one month