An Acute Dose‐Response Pharmacodynamic Evaluation of Orally Administered Isradipine (PN‐200‐110) in Hypertensive Patients

This study was conducted to assess acute oral dose-responses of four dose levels (2.5, 5, 10, 20 mg) of isradipine, a new calcium channel blocking agent of the 1,4-dihydropyridine group. Sixteen patients with mild essential hypertension were investigated using a randomized, four-way cross-over, double-blind, placebo-controlled design. After a 2-week washout period, all patients were admitted to a research unit where they entered a 3-day placebo equilibration, followed by 9 days of double-blind single doses of isradipine. Drug administration was randomized, and baseline blood pressure values obtained preceding active medication doses were fairly constant. Dose-related reductions in supine and in standing blood pressures were obtained. The mean peak supine blood pressure decrements to doses of 2.5, 5, 10, and 20 mg were 17/16, 25/19, 35/22, and 37/25 mm Hg, respectively. Pulse rates increased slightly. Similar responses were obtained with patients in the erect position. Peak hypotensive responses occurred within 3 hours after dosing. The duration of effect persisted as long as 21 hours, particularly after the 10- and 20-mg doses (15/9 and 17/12 mm Hg mean supine blood pressure decrements, respectively).