ABSTRACT
The influence of chronic perindopril treatment on digoxin pharmacokinetics was investigated in 10 patients with mild chronic heart failure under stable diuretic and digitalis treatment and normal renal function. Digoxin was administered at a dose of 0.125 mg/day (n = 2) or 0.250 mg/day (n = 8). The 24-hour steady-state digoxin profile was assessed before and after concomitant administration of perindopril for 1 month at doses of 2 mg once a day for the first 8 days and 4 mg once a day for the remaining 21 days. Chronic treatment with perindopril produced no significant effect on mean (+/- standard deviation) digoxin serum area under the curve for 24 hours (17.9 +/- 7.4 versus 16.3 +/- 4.4 ng/mL.h), peak digoxin concentration (1.3 +/- 0.54 versus 1.2 +/- 0.36 ng/mL), time to peak concentration (3 versus 4 hours), and apparent oral clearance of digoxin (237.7 +/- 109.6 versus 237.4 +/- 79.5 mL/min). Clinical and biologic tolerance of perindopril was good throughout the study. Chronic administration of perindopril did not alter steady-state digoxin kinetics in patients with mild chronic heart failure and normal renal function, indicating that no adaptation of the digoxin dose is required during co-prescription with perindopril in such patients.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Digoxin/pharmacokinetics , Heart Failure/metabolism , Indoles/pharmacology , Aged , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/metabolism , Digoxin/administration & dosage , Digoxin/blood , Female , Heart Failure/drug therapy , Humans , Indoles/administration & dosage , Indoles/metabolism , Male , Perindopril , Time FactorsSubject(s)
Blood Pressure , Smoking/physiopathology , Adult , Female , Heart Rate , Humans , Magnoliopsida , Male , Middle Aged , Plants, Toxic , NicotianaABSTRACT
1. The pharmacokinetics of single oral doses of 20 mg lisinopril and 0.25 mg digoxin, given alone and together, have been studied in 12 normal young male volunteers. 2. Peak serum conc of lisinopril occurred at 6 to 8 h and were slightly higher during combined treatment. Subsequent elimination proceeded moderately rapidly in both cases, concn declining to approx. 25% of peak values in 24 h. The AUC of lisinopril was similarly slightly higher during combined treatment. 3. After lisinopril alone, urinary elimination of unchanged lisinopril was 13% dose in 72 h, and after combined therapy was 17% dose. 4. Although there were no statistically significant differences in lisinopril pharmacokinetics during single or combined treatment, serum and urinary parameters suggest that bioavailability may be enhanced slightly during combined treatment. 5. Plasma concentrations of digoxin were slightly lower and urinary excretion slightly higher during combined treatment, the mean renal clearance being 20% higher.
