The role of regulatory factor for the determination of dosage of digoxin and other drugs in patients with renal dysfunction

Hippokratia 2004, 8(2):73-77

A Efstratopoulos, N Ioakimidis, N Marougas, D Dimou, Th Gialernios, N Karbouniaris
3rd Medical Dpt & Hypertension Unit, General Hospital of Athens “Gennimatas’, Athens, Greece


Background: In cases of chronic renal dysfunction, the dose of drugs that are excreted mainly from the kidneys should be adjusted according to the level of renal function. In such cases, the use of a regulatory factor (RegF) is of clinical importance. In the present work a RegF was calculated from the glomerular filtration rate (GFR) of the patient (Gault -Cockroft method), in relation to normal GFR (120 ml/min/l.73m2 of body surface area), taking into account the body weight, age, sex of the patient and the renal (%) excretion of the drug. The dose based on calculation of RegF was estimated by either the division of the daily dosage or the multiplication of the interval of administration. In our study we used the RegF to estimate the proper dose of digoxin in patients with heart failure or atrial fibrillation, in order to achieve therapeutic plasma levels.
Patients and Methods. A total of 29 patients (14 M / 15 F, 52-92 years-old) with either heart failure or atrial fibrillation, were included in the study. In every patient, digoxin plasma levels were measured initially (following the initial dosage of the drug) and later, after dosing adjustment based on RegF. In every patient, serum creatinine, body weight, GFR and blood pressure were determined. One-way analysis of variance (ANOVA) was used to compare responses following dosing modification due to regulatory factor.
Results: The initial plasma digoxin levels (i.e. plasma levels obtained from the initial dosage) ranged from 0.56 to 3.88 ng/mL (1.63±0.18 ng/mL, M±SE), while, the normal plasma levels ranged from 0.7 to 2.0 ng/mL. Plasma digoxin levels after dosage adjustment according to calculation of the regulatory factor ranged from 0.75 to 2.0 ng/mL (1.17±0.076), (in relation to the initial plasma levels, P: 0.02). Following the initial dosage, 7 patients had toxic digoxin plasma levels, 3.06±0.24, (range 2.14 – 3.88), whereas, after dosage modification, nobody from this study group had toxic plasma levels (i.e. > 2.0 ng/mL) (p < 0.001).
Conclusions. We conclude that the use of RegF to determine the appropriate dosage of digoxin leads to the proper therapeutic plasma levels of digoxin, avoiding the unwanted higher plasma levels of digoxin in patients with heart failure or atrial fibrillation.