Metformin-Dipyridamole Interaction Trial

Study Overview
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Brief Summary
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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.

Official Title
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The Effect of Dipyridamole on the Pharmacokinetics of Metformin

Conditions
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Diabetes

Intervention / Treatment
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* Drug: Metformin, dipyridamole
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin therapy with concomitant use of dipyridamole<br>Metformin 500 mg twice daily for four days in combination with dipyridamole 200 mg twice daily for four days | Drug: Metformin, dipyridamole<br>* Metformin 500 mg twice daily for four days Dipyridamole 200 mg twice daily for four days<br>|
| Active Comparator: Metformin therapy<br>Metformin 500 mg twice daily for four days | Drug: Metformin<br>* Metformin 500 mg twice daily for four days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Effect Dipyridamole on pharmacokinetics of metformin