Therapeutic Serum Digoxin Concentration: Relation to Age, Weight, Sex, and Serum Creatinine Levels‡‡

Abstract

Summary: Serum digoxin concentration was determined by radioimmuno‐assay in a group of 41 hospitalized adult patients (22 males and 19 females), selected prospectively for constant effective dosage with digoxin for at least three weeks, without clinical or electrocardiographic evidence of digoxin intoxication. Serum creatinine values were within the normal or near‐normal range. The majority were receiving diuretic therapy which was associated with mild alkalosis (75% of patients) and occasionally hypomagnesaemia (18%). The patients were considered to be effectively digitalized. The mean serum digoxin concentration six hours after the morning oral dose of digoxin in 28 of the 41 patients, with normal serum creatinine values, was 1.3 ng/ml (S.D. 0.4 ng/ml), and in the other 13 patients with mildly elevated serum creatinine values (range 1.3 to 1.6 mg/dl for 6 males and 1.1 to 1.4 mg/dl for 7 females) was 1.4 ng/ml (S.D. 0.7 ng/ml). Approximate GFR (% of normal corrected for age and surface area) was derived from auto‐analyzer serum creatinine values, using the formulae 110/serum creatinine concentration (mg/dl) for males and 85/serum creatinine for females. The patients with mild renal failure (approximate GFR, males 85 to 69% of normal; females, 77 to 61% of normal) were found to be significantly older and required significantly smaller oral maintenance doses of digoxin than the patients with normal serum creatinine valuestoachieve virtually the same serum digoxin concentration. Formulae were derived to enable calculation of the therapeutic daily dose of digoxin from age in years (A), weight in kg (W), sex and serum creatinine concentration in mg/dl (SCr) as follows:—

Digitalis Therapy in a 70‐Year‐Old Population

“…These changes are often not reflected in alterations in S-creatinine levels, making them dificult to estimate in clinical routine. Renal impairment especially influences the dose tolerance of digoxin (3,9,25,30,31). In the present study, however, no difference in the frequency of symptoms which might indicate digitalis overdosage was observed between patients treated with digoxin and digitoxin.…”

“…At high age, symptoms like dyspnoea and lowered physical capacity may indicate heart disease but may also be signs of normal ageing processes which presumably are not influenced by digitalis therapy. A changed susceptibility to digitalis at high age might be due to, e.g., altered intestinal absorption (7, 10, 21), drug interaction and binding capacity of plasma proteins (14, 27), reduced body cell mass (5, 25), lowered potassium or magnesium concentrations (12,17,26), altered hepatic (15,161 and renal function (3,19,25,30,31), advanced heart disease (1,4,18) and chronic or acute pulmonary disorders (1,8).…”