Evaluation of pharmacokinetic interactions between the antidiabetic metformin andthe antibiotic trimethoprim.

Phase 1

• Conditions: E11.90

• Registration Number: DRKS00000481
• Lead Sponsor: niversität Heidelberg, Medizinische Fakultät

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-13
• Study Completion: 2011-03-10
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Good state of health
- Voluntarily signed informed consent
- No clinically relevant findings in any of the investigations of the pre-study examination, especially estimated creatinine clearance > 60 ml/min (Cockcroft & Gault equation)
- Known genotype for MATE1 and OCT2 polymorphisms from a previous study
- Agreement to abstain from alcoholic beverages during the time of the study.
- Females must agree to a reliable contraception (Pearl Index <1%), e.g. double barrier method.

Exclusion Criteria

- Any regular drug treatment within the last two months with the exception of oral contraceptives in female volunteers and L-thyroxine.
- Any intake of a substance known to inhibit drug metabolising enzymes or drug transporters within a period of less than 10 times the respective elimination half-life.
- Any intake of a substance known to induce drug metabolising enzymes or drug transporters within the last two weeks (e.g. St. John’s Wort).
- Any acute or chronic illness or clinically relevant findings in the pre-study examination.
- Creatinine clearance < 60 ml/min as estimated with the Cockcroft & Gault equation.
- Diabetes mellitus (any type).
- Contraindication against metformin or trimethoprim and any known intolerance to one of the substances or their composites.
- History of multiple and recurring allergies or allergy to the study drugs or to one of its constituents.
- Regular smoking.
- Alcohol abuse (more than approximately 20 g alcohol per day).
- Positive drug screening or known or admitted drug abuse.
- Known or planned pregnancy or breast feeding.
- Blood donation or participation in a clinical trial within the last two months.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Effect of trimethoprim on metformin drug clearance (comparison of metformin steady-state plasma clearance with and without trimethoprim).

Secondary Outcome Measures

Name	Time	Method
Effect of trimethoprim on other pharmacokinetic parameters of metformin (e.g. half-life, apparent volume of distribution, renal clearance).<br>Effect of common polymorphisms in OCT2 and MATE1 genes on the extent of the interaction between trimethoprim and metformin (i.e. reduction of metformin clearance).