Pharmacokinetics and pharmacodynamics of urapidil in severe hypertension.

The clinical response and pharmacokinetics of intravenous urapidil were studied in patients with uncontrolled severe hypertension. Six of nine patients achieved a diastolic blood pressure (DBP) of 100 mm Hg after initial administration of serial bolus doses and were then placed on maintenance infusions. Three of these six patients maintained a DBP 100 mm Hg or lower at infusion rates of 10 to 20 mg/hr, whereas the remaining three patients experienced a loss of DBP control despite rates of 40 mg/hr. Mean DBP was significantly reduced from 126 +/- 6 mm Hg (N = 9) to 105 +/- 15 mm Hg after the bolus phase (N = 9, P less than .05) and 99 +/- 18 mm Hg after the infusion phase (N = 6, P less than .05). Significant reductions in systolic blood pressure were also achieved after bolus and infusion phases. Adverse reactions included drowsiness, tachycardia, nausea and vomiting but were considered mild. Estimated pharmacokinetic parameters included Vz (0.80 +/- 0.20 L/kg), CL (2.53 +/- 0.99 mL/min/kg) and t1/2 (4.0 +/- 1.5 hr). Urapidil safely reduces blood pressure in patients with severe hypertension. An alternative dosing regimen is suggested.