Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy Ajith Munasinghe Dissanayake, Mark Christopher.

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Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy Ajith Munasinghe Dissanayake, Mark Christopher Wheldon, Jafar Ahmed, Christopher John Hood Kidney International Reports Volume 2, Issue 4, Pages 705-712 (July 2017) DOI: 10.1016/j.ekir.2017.03.005 Copyright © 2017 International Society of Nephrology Terms and Conditions

Figure 1 Study design. CGMS, 72-hour capillary glucose monitoring; Safety profile—serum lactate, bicarbonate, venous pH, renal function and electrolytes, liver enzymes, and full blood count. Kidney International Reports 2017 2, 705-712DOI: (10.1016/j.ekir.2017.03.005) Copyright © 2017 International Society of Nephrology Terms and Conditions

Figure 2 Safety profile (venous lactate, bicarbonate, and pH) in all 3 cohorts across the study period. Venous lactate for patient 11 appears as a dotted line. Patients 2 and 19 commenced metformin therapy a few days after enrollment in study. Kidney International Reports 2017 2, 705-712DOI: (10.1016/j.ekir.2017.03.005) Copyright © 2017 International Society of Nephrology Terms and Conditions

Figure 3 Pharmacokinetic profiles in all 3 cohorts across the study period. The first graph represents the 24-hour concentration-time curve after the first dose of metformin. The dotted lines are observed patient values. The solid line represents a fitted curve for a first-order compartment model with absorption in the peripheral compartment. The second graph represents all trough concentrations at a steady state over 4 weeks. The actual and mean values are presented as dotted and solid lines, respectively. Number labels represent patients in the trial. conc., concentration. Kidney International Reports 2017 2, 705-712DOI: (10.1016/j.ekir.2017.03.005) Copyright © 2017 International Society of Nephrology Terms and Conditions