Inter- and Intra-individual Variations in Metformin Pharmacokinetics - The Importance of Genes and Drug Interactions

• Status: Completed
• Trial end date: 2020-06-13
• Target enrollment: 0
• Participant gender: All

Summary

The investigators aim to investigate the interindividual variation in metformin AUC in a large cohort of healthy volunteers after a single dose of metformin. Part 1 is driven by the hypothesis that metformin AUC and renal clearance exhibit significant interindividual variation. However this has never been documented in a large cohort of healthy volunteers.

The investigators aim to investigate the potential interaction between codeine and metformin in the intestine. The hypothesis underlying part 3 is that the increased risk of early discontinuation of metformin during co-administration with codeine is primarily due to local inhibition of OCT1 via codeine at the intestinal level.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Southern Denmark
• Treatments: Codeine; Metformin

Criteria

Inclusion Criteria Part 1 (and 2): Men and women. Apparent good general health. eGFR, creatinine, Hba1c, must be within the reference range or clinically insignificantly differ from this. Written consent must be given. Age 18-65. BMI 18,5 - 29,9kg/m².

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Exclusion Criteria part 1 (and 2): Daily consumption of medicine (prescription, over the counter and herbal medicines, dietary supplements (oral contraceptives and regular vitamin pills are accepted)). Alcohol abuse. Hypersensitivity for metformin. For women: positive pregnancy test and not using safe contraceptives for 24 hours after intake of metformin and breastfeeding.

Inclusion Criteria Part 3:Apparent good general health. eGFR, creatinine, Hba1c, glucose, ALAT and bilirubin must be within the reference range or clinically insignificantly differ from this. Written consent must be given. Age 18-30 . BMI 18,5 - 29,9kg/m².

Exclusion Criteria part 3: Daily consumption of medicine (prescription, over the counter and herbal medicines, dietary supplements (regular vitamin pills are accepted)). Alcohol abuse. Hypersensitivity for metformin, codeine or morphine. Genetically proven CYP2D6 slow or ultra-fast metabolizers. Genetically proven loss-of-function allele in OCT1

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