Efficiency of individual dosage of digoxin with calculated concentration

BACKGROUND: Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4-1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8-2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC. METHODS: The study subjects comprised 72 patients with cardiac failure or/and atrial tachyarrhythmia seen at our hospital from January 2012 to December 2013. The patients were divided into five groups according to Kidney Diseases Outcome Quality Initiative guidelines. SDCs were measured using the Abbott Architect i1000 immunology analyzer. The correlations between measured SDCs and calculated SDCs and between clearance of digoxin and creatinine clearance rate were assessed retrospectively. RESULTS: The correlation between measured and predicted SDC calculated by the Konishi equation was significant (r=0.655, P<0.001) for the 72 patients overall; however, correlations within the different stages of renal function were nonsignificant, with a correlation found only in patients with stage 3 (30 mL per minute < creatinine clearance <60 mL per minute). With regard to the correlation between clearance of digoxin and creatinine clearance, our results show that although there was a significant correlation between clearance of digoxin and creatinine clearance in the group overall, correlations were not evident within the different stages of renal function. CONCLUSION: The results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease. Further research in larger numbers of patients across all stages of renal function will be required in the future to verify the original Konishi model.