Pharmacokinetics of digoxin in patients with atrial fibrillation: role of the classic co-variables

This work was performed to study the pharmacokinetics of digoxin in patients suffering from atrial fibrillation [AF] after optimization of all the known classic factors contributing to inter-patient variability in serum digoxin levels, to detect if any variability in serum digoxin levels still exists or this variability is only a function of the classic co-variables so that their optimization will diminish or eliminate it. Twenty male patients suffering from AF, were selected from the Critical Care Medicine Department, Cairo University Hospitals to be enrolled in the study. A patient is initially considered to be a candidate for this study when digoxin therapy was indicated. Patients were selected to have non-significant variations in their demographics and pretreatment clinical data. Blood samples were drawn from each patient at specified intervals and the serum fractions were separated and assayed for digoxin, using digoxin enzyme multiple immunoassay technique [Emit 2000]. The results revealed unpredictable variability in serum digoxin levels among patients at each sampling time and a marked inter-patient variability in mean serum digoxin levels among individuals throughout the twenty four hours, [P value: 0.0001].Considerable inter-patient variability was also evident in digoxin pharmacokinetics. Digoxin was rapidly absorbed after dosage administration, with C[max] occurring at 0.5 to 1.0 hour in all patients. Mean T[max] was 0.575 +/- 0.18 hr. Digoxin C[max] varied from 0.86 to 6.72 ng/ml with a mean value of 3.99 +/- 1.91 ng/ml. AUC also varied greatly among patients [from 6.16 ng hr/ml to 112.14 ng hr/ml] with a mean value of 49.47 +/- 30.344 ng/hr/ml. The elimination half-life [t[1/2]] varied from 0.86 days to 7.16 days with a mean value of 2.66 +/- 1.45 days. The overall mean oral clearance also showed a great variability among patients with a mean of 9.3 +/- 8.7 ml/hr/kg [CV: 92.9%]. In conclusion: variability in serum digoxin concentrations and digoxin pharmacokinetics existed in spite of careful patient selection and optimization of all the classic co-variables known to affect digoxin concentrations, suggesting the presence of other unstudied factors; the recently evolving genetic factors might contribute to this variability