Metformin-Dipyridamole Interaction Trial (MetDipy)

• The area under the curve of the metformin plasma concentration at several timepoints [ Time Frame: 10 hours after ingestion of last dose of metformin ] [ Designated as safety issue: No ]
  The area under the curve of the metformin plasma concentration at t=0, t=1, t=2, t=2.5, t=3, t=3.5, t=4, t=5, t=6, t=8, and t=10 hours after the intake and the Cmax.
• Peak plasma concentration (Cmax) of metformin [ Time Frame: about 3 hours after intake of last dose of metformin ] [ Designated as safety issue: No ]
  Peak plasma concentration (Cmax) of metformin

The antihyperglycemic drug metformin and the thrombocyte aggregation inhibitor dipyridamole are often used concomitantly in patients with diabetes who have suffered a transient ischemic attack or stroke. It has recently been suggested that the gastrointestinal absorption of metformin is mediated by the equilibrative nucleoside transporter 4 (hENT4). Dipyridamole has been reported to inhibit hENT4 transport in vitro. The aim of this research proposal is to study the pharmacokinetic interaction between metformin and dipyridamole. The investigators hypothesize that dipyridamole reduces the gastrointestinal absorption of metformin. If this hypothesis can be confirmed, then the results of this study can explain in part the high variability in plasma metformin concentrations in patients treated with diabetes, and can be used to optimize pharmacotherapy in patients with diabetes.

• Drug: Metformin, dipyridamole
  Metformin 500 mg twice daily for four days Dipyridamole 200 mg twice daily for four days
• Drug: Metformin
  Metformin 500 mg twice daily for four days

• Active Comparator: Metformin therapy with concomitant use of dipyridamole
  Metformin 500 mg twice daily for four days in combination with dipyridamole 200 mg twice daily for four days
  Intervention: Drug: Metformin, dipyridamole
• Active Comparator: Metformin therapy
  Metformin 500 mg twice daily for four days
  Intervention: Drug: Metformin

Inclusion Criteria:

• Age 18-50 years
• Written informed consent

Exclusion Criteria:

• Smoking
• Hypertension (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg)
• Diabetes Mellitus (fasting glucose >7.0 mmol/L or random glucose >11 mmol/L)
• History of any cardiovascular disease
• Concomitant use of medication
• Renal dysfunction (MDRD <60 ml/min)
• ECG abnormalities, other than firs grade AV-block or right bundle branch block