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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin therapy with concomitant use of dipyridamole | Active Comparator | Metformin 500 mg twice daily for four days in combination with dipyridamole 200 mg twice daily for four days |
|
| Metformin therapy | Active Comparator | Metformin 500 mg twice daily for four days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin, dipyridamole | Drug | Metformin 500 mg twice daily for four days Dipyridamole 200 mg twice daily for four days |
|
| Measure | Description | Time Frame |
|---|---|---|
| The area under the curve of the metformin plasma concentration at several timepoints | 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. | 10 hours after ingestion of last dose of metformin |
| Peak plasma concentration (Cmax) of metformin | Peak plasma concentration (Cmax) of metformin | about 3 hours after intake of last dose of metformin |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| N. Riksen, MD, PhD | Radboud University Medical Center | Principal Investigator |
| G. Rongen, MD, PhD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Nijmegen Medical Centre | Nijmegen | Gelderland | 6500 HB | Netherlands |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| D004176 | Dipyridamole |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D011743 |
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| Metformin | Drug | Metformin 500 mg twice daily for four days |
|
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |