A Simple Index for the Determination of Digoxin Dosage for the Patients with Various Renal Functions.

Abstract

To elucidate the current status of the dosage regimen of digoxin (DX), we reviewed its therapeutic drug monitoring (TDM) data obtained from 50 patients on whom TDM was performed for the first time following the beginning of DX treatment. The serum trough level of DX in 50% the subjects deviated from its therapeutic range (0.5-1.5 ng/ml) because the uniform dosage (0.125-0.148 mg/day) was administered for the patients with various degrees of renal functicns. The serum levels of DX in about 70% of the patients with normal renal function (80 ml/min creatinine clearance. CLcr) were less than its lower limit (0.5 ng/ml), and those in about 70% of patients with severe abnormal renal function (CLcr<40 ml/min) exceeded its upper limit (1.5 ng /ml).To design a simple index for the dosage regimen of DX whith closely corresponded to the renal functions in patients, 286 samples of TDM data obtained from 87 patients who were not coadministered drugs known to alter DX pharmacokinetics were reviewed by dividing then into three groups according to the CLcr values. The mean serum DX levels (0.7-1.2 ng/ml) in each group could be kept at their therapeutic range, as the dosages were respectively 0.25 mg/day (80 CLcr group), 0.125-0.25 mg/day (40<CLcr<80 group), or 0.0625-0.125 mg/day (CLcr< 40 group). These results indicate that the minimum dosages of DX in each reual function group, which were expected to maintain its effective serum level (0.7 ng/ml) within the lower limit of the therapeutic range, are desirable from a safety, that is, the optimal dosages of DX as an indication in the early dosing stage are respectively 0. 25 mg/day for patients with normal renal function (80 CLcr), 0.125 mg/day for patients with moderate abnormal renal function (40<CLcr< 80), and 0.0625 mg/day for patients with severe abnormal renal functicn (CLcr<40).

Predictive performance of serum digoxin concentration in patients with congestive heart failure by a hyperbolic model based on creatinine clearance

“…A Bayesian feedback approach has been used for determining the optimal dosing regimen of digoxin for an individual patient, but this method requires the actual measurement of serum digoxin (22). Therefore, a simple starting guideline for rapid determination of the dose requirement is desired in clinical practice (5), particularly in an emergency situation. As the elimination rate of digoxin shows a linear dependence on renal function (6), it is necessary to evaluate the Ccr as a dominating factor in predicting serum digoxin concentration.…”

“…Because of the narrow therapeutic index and the need for long‐term treatment, measurement of serum digoxin concentration is recommended in order to maximize the therapeutic effects and avoid adverse events such as nausea, vomiting, visual disorder and arrhythmias (4). However, careful choice of the initial and maintenance dose is essential (5). As digoxin is eliminated mostly unchanged by the kidney, and only a small proportion being metabolized or excreted via the biliary route, renal function is the primary determinant of the pharmacokinetic behaviour of digoxin (6).…”