[Antihypertensive effect and tolerance to urapidil. Comparison with nifedipine in a multicenter double-blind study]. / Antihypertensive Wirksamkeit und Verträglichkeit von Urapidil. Multizentrische Doppelblind-Studie im Vergleich zu Nifedipin.

In a multi-center, double-blind parallel-group study involving patients with essential hypertension (grade I/II), the antihypertensive effect and toleration of the postsynaptic alpha-1 receptor blocker, urapidil, was compared with that of the calcium antagonist, nifedipine. After a one-week wash-out, and one week period on placebo, the patients received either urapidil 60 mg in the morning and evening (n = 81), or nifedipine retard 20 mg mornings and evenings (n = 87), over a period of 12 weeks. The results show that urapidil and nifedipine administered alone, produce an effective lowering of blood pressure. The reduction in systolic blood pressure-approximately 12 hours after the last administration-was, on average, 10 mmHg for urapidil, and 14 mmHg for nifedipine. The reduction in systolic blood pressure was more marked under nifedipine (19 mmHg) than under urapidil (10 mmHg). The difference in heart rate at the end of the treatment phase did not differ significantly from the pre-treatment figure with either drug. The 12-week treatment with urapidil and nifedipine had no effect on lipid metabolism. Fourteen patients receiving urapidil, and 24 patients on nifedipine complained of undesirable side effects (in particular headaches and giddiness). Flushing occurred only in the nifedipine group. 8 patients on urapidil and 3 on nifedipine discontinued due to side effects.

Permeation of the blood-brain barrier by urapidil and its influence on intracranial pressure in man in the presence of compromised intracranial dynamics.

We studied eight patients undergoing craniotomy for intracerebral tumour surgery requiring monitoring of intracranial pressure. All these patients showed significantly increased systolic arterial pressure, during anaesthesia. Following an average dose of 0.8 +/- 0.22 mg/kg urapidil, systolic arterial pressure returned to baseline values without a significant change in intracranial pressure. In nine patients, urapidil concentrations in plasma and cerebrospinal fluid were assayed following an intravenous injection of urapidil. Urapidil was found in the cerebrospinal fluid in concentrations between 5 and 99 ng/ml after total cumulative bolus injections of 10-75 mg. There is evidence that in clinically applied doses urapidil permeates the blood-brain barrier and reaches cerebrospinal fluid concentrations that allow an interaction with central 5-hydroxytryptamine-1A receptors.

Efficacy of once-daily urapidil treatment in mild or moderate essential hypertension assessed by ambulatory 24-hour blood pressure monitoring.

The blood pressure-lowering effect and tolerability of urapidil 120 mg once daily versus urapidil 60 mg twice daily was compared in 36 outpatients with newly diagnosed mild to moderate essential hypertension. Patients were enrolled in the study if they showed a favourable response to urapidil 60 mg twice daily at the end of a 2-week run-in as revealed by a first non-invasive 24-hour blood pressure profile. The patients were then randomly allocated to a 6-week double-blind treatment with either urapidil 120 mg once daily or urapidil 60 mg twice daily. Blood pressure, heart rate and adverse reactions were recorded every 2 weeks in the morning before drug intake. A second 24-hour blood pressure profile was taken at the end of this treatment phase. Compared with the pretreatment value after placebo run-in, urapidil 60 mg twice daily lowered supine morning blood pressure from 159/103 to 138/89. Urapidil 120 mg once daily lowered blood pressure from 161/102 to 139/90. The decrease in blood pressure was statistically significant within (p less than 0.001) but not between the treatment groups. Similar results were obtained with standing blood pressures. Side effects were observed in 2 patients with urapidil 60 mg twice daily (dizziness, intermittent lack of ejaculation) and in 7 patients with urapidil 120 mg once daily (5 with dizziness, and 1 each with headache and palpitations). Thus, urapidil 120 mg once daily lowers elevated blood pressure throughout a 24-hour period as effectively as 60 mg twice daily. Therefore, during long term therapy, the tolerability but not the efficacy of urapidil appears to be directly related to its peak serum concentrations.