EFFECTS OF LONG-TERM ORAL CARVEDILOL ON THE STEADY-STATE PHARMACOKINETICS OF ORAL DIGOXIN IN PATIENTS WITH MILD-TO-MODERATE HYPERTENSION

The effect of multiple oral doses of carvedilol on steady-state plasma digoxin pharmacokinetics was evaluated in 12 patients with mild to mo derate hypertension. Area under the curve (AUC), mean maximum plasma c oncentration (C-max), mean lime to maximum concentration (T-max), conc entration at 24 hours after the dose (C-24), creatinine clearance, ren al digoxin clearance, and urinary digoxin excretion were determined al ter patients took oral digoxin 0.25 mg once/day for 2 weeks. Carvedilo l was added to the regimen, and digoxin pharmacokinetics were assessed after 2 weeks of concurrent treatment. The AUC and C-max for digoxin increased by 14 % and 32%, respectively (p<0.05), with no change in T- max. The 24-hour urinary digoxin excretion and 24-hour renal digoxin c learance increased by 45% and 26%, respectively (p<0.05), with no chan ge in creatinine clearance. Carvedilol appears to increase digoxin's o ral bioavailability as well as renal elimination. The absolute change in digoxin pharmacokinetics was small and not clinically significant. The significance of the interaction in other patient populations remai ns to be studied.