Four periods of oral dosing following overnight fasting (1. known metabolic probe drug cocktail consisting of caffeine, diclofenac, esomeprazole, metoprolol, midazolam; 2. dabigatran + cocktail; 3. dabigatran alone; 4. clarithromycin 3 days + cocktail + dabigatran). Blood samples collected for pharmacokinetics over 24 h. Washout between periods. Adverse events, haematology and clinical chemistry recorded.

Inclusion Criteria:

• Healthy
• Weight at least 50 kg and body mass index 19 - 30 kg m-2
• Normal clinical laboratory profiles
• No childbearing potential or use of adequate contraceptive measures

Exclusion Criteria:

• Blood loss >300 ml within 2 months prior to the first dosing day
• Pregnancy, breastfeeding
• Allergy or hypersensitivity to caffeine, diclofenac, esomeprazole, metoprolol, midazolam, dabigatran or clarithromycin or to excipients in the pharmaceutical products
• Infection with HIV, HBV or HCV
• Participation in the preceding 3 months or concomitantly in any clinical drug study
• Suspected current drug or alcohol abuse
• History of drug or alcohol abuse.
• Concomitant medication with the exception of hormonal contraception.
• Positive result in urine test for drug abuse.
• Nicotine consumption equivalent to >5 cigarettes per day