Comparative pharmacokinetics and pharmacodynamics of lisinopril and enalapril, alone and in combination with propranolol

Abstract

In an open, crossover study, the pharmacokinetic and pharmacodynamic profiles of lisinopril and enalapril, administered alone and in combination with propranolol, were evaluated in 12 volunteers. The maximum serum concentration (C(max)) of lisinopril and time to reach maximum concentration (T(max)) were 64 ± 16 ng/ml and 7.5 ± 1.5 h, respectively. The area under the surum curve (AUC) was 916 ± 239 h. ng/ml. The C(max) of enalaprilat (89 ± 34 ng/ml) was greater than that of lisinopril whilst T(max) was shorter (4.3 ± 1.7 h) and AUC smaller (718 ± 17 h. ng/ml)(P < 0.01). Renal clearance of drug 48 h post-dosing showed that enalaprilat (164 ± 38 ml/min) was cleared from plasma significantly more rapidly than lisinopril (82 ± 16 ml/min)(P < 0.001). Mean supine blood pressure decreased significantly with all treatments, as did heart rate. No significant changes were observed in either the serum concentrations or the urinary outputs of these ACE inhibitors following combination with propranolol, apart from a greater variability of C(max) after addition of propranolol to enalapril compared with lisinopril in combination.