T PUTT1, J SCHOLLUM1, R WALKER1, J LEISHMAN1, S DUFFULL2, D WRIGHT2
1Department of Medicine, University of Otago, Dunedin, NZ; 2School of Pharmacy, University of Otago, Dunedin, NZ
Aim: To investigate the Pharmacokinetics of Metformin in advanced kidney disease.
Background: Metformin is the first line therapy for patients with Type 2 diabetes to achieve glycaemic control and has demonstrated a substantial beneficial effect on cardiovascular disease (CVD) outcomes. Current recommendations for Metformin prescribing is to dose with caution when the eGFR is <60 ml/min/1.73m2 and discontinue when the eGFR less than 15ml/min/1.73m2
Drug dosing recommendations in the setting of renal impairment make the assumption that the drug is fully cleared by glomerular filtration and that tubular mechanisms of clearance and secretion decline at the same rate as GFR. In previous studies, we have demonstrated that drug clearance by organic cation transport (OCT) does not parallel GFR. As Metformin is renally excreted via OCTs, dose adjusting according to GFR may not be appropriate. To date there is no data on Metformin’s clearance in patients with Stage 4-5 kidney disease.
Methods: We assessed the pharmacokinetics of a single dose Metformin (500mg) in CKD 4-5 patients, compared with normal controls. Renal clearances were determined by creatinine clearance, gentamicin clearance (as an alternate marker of GFR) and metformin clearance over the following 24 hours.
Results: There was no difference in the 24-hour excretion of metformin in either group. The mean values were: controls 164mg/24hr vs CKD 4-5 134mg/24hr (p=0.09). Of interest the peak concentration of metformin post ingestion was almost double in the CKD group suggesting differences in absorption that may be clinically relevant and require further investigation.
Conclusions: Metformin pharmacokinetics in advanced CKD have not previously been well studied. Although there may be differences in absorption, actual clearances do not seem to be altered in CKD.