Pharmacodynamic and pharmacokinetic studies with the vasodilator endralazine

Endralazine is a peripherally-acting vasodilator similar to hydralazine. In normotensive subjects and essential hypertensive and renal patients, single oral doses of 10 mg endralazine led to substantial falls in blood pressure, with no significant additional orthostatic effect. Maintenance endralazine treatment (5 or 10 mg b.d.) of essential hypertensive patients significantly improved blood pressure control: the mean supine blood pressure improved from 197/107 mmHg on baseline treatment with a thiazide and beta-blocker to 160/86 mmHg after one week and 161/91 mmHg after one year. There was no evidence of fluid retention and in all patients treated for at least one year the anti-nuclear factor remained negative. Following acute administration the terminal elimination half-life of endralazine was approximately 2.5 h and the oral bioavailability was 75%. During chronic treatment the elimination half-life significantly increased to about 7.5 h. The elimination half-life following the first dose was only significantly prolonged in the renal dialysis group. There were no significant differences related to acetylator phenotype.