Glomerular filtration rate estimation using the Cockcroft-Gault and Modification of Diet in Renal Disease formulas for digoxin dose adjustment in patients with heart failure

OBJECTIVE: The aim of this study was to compare the estimated glomerular filtration rate (GFR) using the Cockcroft-Gault and the 4-, 5-, and 6-variable Modification of Diet in Renal Disease (MDRD) formulas for digoxin dose adjustment. METHODS: Steady-state serum digoxin concentrations were determined in 100 patients with heart failure and normal to severely impaired renal function. Total clearance (CL) and predicted average concentrations of digoxin were calculated using general pharmacokinetic principles. RESULTS: The mean±SEM (median) estimated GFR values were 48.9±2.8 (46.5) mL/min/1.73 m(2) using the Cockcroft-Gault formula, 61.4±3.6 (56.4) mL/min/1.73 m(2) using the MDRD4 formula, 56.8±3.3 (52.1) mL/min/1.73 m(2) using the MDRD5 formula, and 53.3±3.0 (48.7) mL/min/1.73 m(2) using the MDRD6 formula, with high correlation coefficients between the estimates (r≥ 0.928, P<0.001). Significant correlations were found between the digoxin total CL and estimated GFR by the Cockcroft-Gault (r=0.649, P <0.001), MDRD4 (r=0.634, P <0.001), MDRD5 (r=0.635, P<0.001), and MDRD6 (r=0.652, P <0.001) formulas. A significant negative correlation of the digoxin total CL/GFR ratio with estimated GFR was obtained (r= −0.356, P<0.001), with a high variability for this ratio for GFR lower than 60 mL/min. Analogous correlation coefficients were found between the obtained and predicted digoxin concentrations calculated using the estimated GFR by the Cockcroft-Gault (r=0.628, P <0.001), MDRD4 (r=0.642, P <0.001), MDRD5 (r=0.650, P <0.001), and MDRD6 (r=0.665, P <0.001) formulas, with a wide dispersion between the values in all cases. CONCLUSION: For GFR lower than 60 mL/min, the high interindividual variation of the digoxin total CL found among patients with similar renal function is an important limiting factor in the prediction of digoxin dosage regimens.