In an open monocentric phase II study, 20 inpatients with hypertension were treated with a single daily dose of nilvadipine for 3 weeks after a 1-week placebo washout phase. The initial dose in all patients was 8 mg/day p.o.; this was doubled to 16 mg once daily if an adequate blood pressure reduction was not achieved after 10 days on 8 mg. The objective of the study was to investigate the effect of this new calcium antagonist on the blood pressure in hypertensive patients. This was done by means of a 24-h blood pressure profile (with measurements at 0.5, 1, 2, 4, 8, 12, and 24 h after administration), and over the complete course of the treatment period (blood pressure measurements each day just before the medication was given). In addition, by determination of the nilvadipine plasma levels on the first, tenth, and last medication day, a possible concentration-efficacy relationship was to be ascertained between plasma concentration of nilvadipine and the observed blood pressure-lowering effect of the drug. Adequate blood pressure reductions were achieved with nilvadipine 8 mg once daily in 13 patients; 7 required a doubling of the dosage to 16 mg/day. Already on the first day of therapy, both the systolic and diastolic blood pressures were significantly reduced compared to those in the placebo phase (p < 0.001). When comparing the last placebo day and the first medication day, an additional, even more marked lowering of the mean blood pressure could be demonstrated after 24 h; the systolic values fell from 182.1 ± 11.5 to 161.4+ 13.9 mm Hg(p<0.0001) and the diastolic blood pressure from 98.6 ± 3.0 to 88.5 ± 4.5 mm Hg (p < 0.0001). The maximum blood pressure reduction was seen 2 h after the medication was taken on the first as on the last medication day. On the last day of treatment, the mean diastolic blood pressure of the group was under 90 mm Hg at every measurement. All in all, 60% of the hypertensive patients were responders, i.e., their diastolic blood pressure was 90 mm Hg or less 24 h after the final dose of nilvadipine. The plasma levels of nilvadipine rose rapidly to a maximum 2 h after administration on the first day of therapy, and then dropped quickly. A clear deceleration in the fall started 8 h after administration. This happened similarly but at a slightly higher level after 10 and 21 days of therapy. Although it was not possible to show a relationship between the nilvadipine plasma levels and the hypotensive effect, there was still a good correlation between the calculated tissue concentration of the drug and its hypotensive effect. Nilvadipine did not induce reflex tachycardia at either of the dosages (77.9 ± 10.5 compared to 80.6 ± 8.4 beats/min) or to any change in body weight (81.8 ± 16.6 compared to 80.0 ± 15.4 kg). Side effects were only reported by 3 of the 20 patients. The findings indicate that the new calcium antagonist nilvadipine with once-daily dosages is well tolerated and provides effective blood pressure control in patients with mild to moderate hypertension.
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