Metformin-Dipyridamole Interaction Trial (MetDipy)

The Effect of Dipyridamole on the Pharmacokinetics 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.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: Metformin, dipyridamole; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • Radboud University Nijmegen Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Metformin, dipyridamole; Metformin 500 mg twice daily for four days Dipyridamole 200 mg twice daily for four days
Active Comparator: Metformin therapy; Metformin 500 mg twice daily for four days	Drug: Metformin; Metformin 500 mg twice daily for four days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: G. Rongen, MD, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 25, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Estimate): April 29, 2013
• Last Update Submitted That Met QC Criteria: April 26, 2013
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Effect Dipyridamole on pharmacokinetics of metformin
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Phosphodiesterase Inhibitors; Dipyridamole; Metformin
• Other Study ID Numbers: Met-Dipy001