THE BIOAVAILABILITY OF DIGOXIN FROM 3 ORAL FORMULATIONS MEASURED BY A SPECIFIC HPLC ASSAY

1 We have studied the absolute bioavailability of three oral formulations of digoxin, 1.0 mg, in 12 young healthy volunteers in a four way randomised cross-over study using an intravenous control. 2 Digoxin tablets (250 mug), liquid filled digoxin capsules (100 mug) and an experimental enteric-coated capsule (100 mug) were evaluated. In vitro dissolution at pH 1 demonstrated extensive hydrolytic breakdown of digoxin from the tablets and capsules but not from the enteric-coated capsules. 3 Serum 'digoxin' concentrations were measured by fluorescence polarization immunoassay (FPI). The systemic availability (+/- s.d.) of the capsules was 70.5 +/- 11.3%, and that of the tablets 71.5 +/- 8.6%. Drug was less available from the enteric-coated capsules (62.1 +/- 10.3%) measured with FPI. These results were reflected in the urinary drug recoveries measured by FPI. 4 By contrast, there were no differences in urinary recovery of unchanged digoxin between any of the oral treatments, when this was measured by h.p.l.c. The cross-reactivity of immunoassays for metabolites of digoxin may produce artefactual results and the optimal pharmaceutical formulation for digoxin remains to be determined.