Clinical pharmacological studies with the vasodilator endralazine in normotensive subjects and essential hypertensives.

Endralazine is a peripherally-acting vasodilator with chemical and pharmacological similarities to hydralazine. In both normotensive volunteers and essential hypertensives, single oral doses of 10 mg endralazine (in combination with a beta-adrenoceptor antagonist) led to substantial falls in blood pressure, with no significant additional orthostatic effect. Maintenance treatment of hypertensive patients with the addition of 5 or 10 mg B.D. endralazine 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 after one week and 161/91 mmHg after one year with endralazine as third drug therapy. Apart from facial flushing and mild headache following the early doses, no significant side-effects were observed or reported. In the long term, there was no weight gain to suggest fluid retention and in all patients treated with endralazine 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 dosing with endralazine the terminal elimination half-life significantly increased to a mean of 7.5 h, but there was no accumulation of drug. There were no significant differences related to acetylator phenotype either for the dosage, the pharmacokinetics or the hypotensive effect.