E11.90
Conditions
Interventions
Group 1: Oral administration of metformin (Glucophage 500 mg po TID, day 1-10) and trimethoprim (Infectotrimet 200 mg po BID, day 5-10).
Sponsors
Universität Heidelberg, Medizinische Fakultät
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of trimethoprim on metformin drug clearance (comparison of metformin steady-state plasma clearance with and without trimethoprim). | — |
Secondary
| Measure | Time frame |
|---|---|
| Effect of trimethoprim on other pharmacokinetic parameters of metformin (e.g. half-life, apparent volume of distribution, renal clearance). 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). | — |
Countries
Germany
Contacts
Public ContactMarlies Schnetz
Universitätsklinikum Heidelberg, Abteilung Klinische Pharmakologie und Pharmakoepidemiologie
Outcome results
None listed