None listed
Conditions
Brief summary
Metformin is the first-line treatment for Type-2 diabetes. There is currently no clear consensus on the safe prescribing of metformin in patients with impaired renal function and concern that these individuals are at increased risk of serious side effects. The renal handling of metformin in patients with kidney dysfunction is poorly understood. This project aims to clarify the impact of kidney function on metformin renal handling. This information will provide the scientific basis for a revised dosing guideline for patients with renal impairment.
Interventions
The proposed research will be an open label, single dose pharmacokinetic study. Each volunteer will receive a single dose of metformin 500mg orally followed by 7 blood samples over 24 hours. The sampling schedule is based on the known pharmacokinetics of metformin (half life ~ 6 hours) with intensive sampling in the first 2 hours to capture drug absorption, followed by further sampling over 24 hours to capture drug excretion (e.g. 15-30 minutes, 30-60 minutes, 90-120 minutes, 4, 6, 8 and 24 hour
The proposed research will be an open label, single dose pharmacokinetic study. Each volunteer will receive a single dose of metformin 500mg orally followed by 7 blood samples over 24 hours. The sampling schedule is based on the known pharmacokinetics of metformin (half life ~ 6 hours) with intensive sampling in the first 2 hours to capture drug absorption, followed by further sampling over 24 hours to capture drug excretion (e.g. 15-30 minutes, 30-60 minutes, 90-120 minutes, 4, 6, 8 and 24 hours for the measurement of metformin, gentamicin, creatinine (3 samples), urate (3 samples), and cystatin C (1 sample)). Timed urine samples (0-3, 3–8, 8–24 hours) will be collected to determine the renal clearances of metformin, urate, creatinine, and gentamicin. Note that urate will provide a control for tubular function. In addition, we will administer a single dose of gentamicin 40mg by IV injection at the same time as the metformin dose. This a commonly used antibiotic but it being used here as a marker for glomerular filtration rate (GFR). This will provide an accurate ‘control’ for GFR. Subjects will be stratified into 3 groups based on kidney function; eGFR 1) > 60mL/min, 2) >30 and =< 60mL/min, 3) =<30mL/min. This will allow us to quantify the impact of different stages of renal disease on metformin renal handling. We intend to recruit 45 subjects (15/group).
Sponsors
Dr Dan Wright
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects with a measured eGFR either <=30mL/min, between >30 & <= 60mL/min and > 60 mL/min 2. Subjects who are >18 years of age.
Exclusion criteria
1. Subjects who are unable or unwilling to give written informed consent 2. Subjects with Type 2 diabetes or who are currently taking metformin 3. Subjects with evidence of >25% change in eGFR in the past month 4. Significant asthma, heart failure or any condition associated with a fragile fluid balance (potential reaction to beta-blockade) 5. Pregnancy 6. Known allergy to medication classes; biguanides or aminoglycosides. 7. The concomitant use of drugs known or suspected to interact with the tubular transport of metformin or creatinine including: antibiotics (unless a 2 week washout), beta-blockers, calcium channel blockers, antiarrhythmic drugs, H2 blockers, thiazide diuretics (unless a 7 day washout), antituberculosis drugs, and probenecid.
Outcome results
None listed