Changes in the plasma levels and basic pharmacokinetic parameters of digoxin used in combination with gentamicin, amiodarone and spironolactone.

Digoxin was administered intravenously (0.035 mg/kg b.w.). A prior five-day treatment with gentamicin (100 mg/kg b.w., 10 mg/kg b.w., i.m.), amiodarone (30 mg/kg b.w., s.c.) and spironolactone (10 mg/kg b.w., p.o.) caused elevation of plasma digoxin levels primarily because the alpha half-life was prolonged (t1/2 alpha). In a combined five-day application of digoxin with gentamicin (10 mg/kg b.w., i.m.), and of digoxin with amiodarone, the plasma levels of digoxin rose due to the lengthened beta half-life (t1/2 beta). In administering a combination of digoxin and spironolactone, the plasma digoxin levels dropped, t1/2 alpha decreased and t1/2 beta increased. A 15-day digoxin treatment tested combinations of digoxin, from days eight to 15, with gentamicin (10 mg/kg b.w., i.m.); with amiodarone, or with spironolactone. The digoxin level was elevated with the combinations of digoxin-amiodarone and digoxin-spironolactone: t1/2 alpha was longer in both cases, while t1/2 beta was longer only for the digoxin-amiodarone combination. No changes were found in the creatinine clearance or renal histology of experimental animals after treatment, nor were any deviations found in the values of T3, T4 and TTX.