Comparative pharmacokinetics of enalapril and lisinopril, alone and with hydralazine

A singe-blind, crossover study of vasodilator/angiotensin-converting enzyme (ACE) inhibitor interactions was carried out in 16 volunteers. Enalapril 20 mg and lisinopril 20 mg were administered either alone or in combination with hydralazine 25 mg. Co-administration of hydralazine significantly increased the area under the plasma concentration time curve (AUC) of lisinopril (AUC(0-48 h) 766.8 ± 66.3 ng. h/ml (lisinopril) vs 1022.3 ± 115.3 ng. h/ml (lisinopril + hydralazine)). This did not occur with enalaprilat (AUC 710.1 ± 51.2 ng. h/ml (enalapril) vs 681.9 ± 44.9 ng. h/ml (enalapril + hydralazine); mean ± SEM). Urinary recovery of lisinopril showed a similar trend, but group differences did not achieve statistical significance despite comparable confidence intervals. Although hydralazine had no effect on the bioavailability of enalapril, significantly increased bioavailability was observed with lisinopril. This type of drug interaction is rare. The underlying mechanism is unclear, but may relate to increased absorption of lisinopril.