TIME DEPENDENCY OF THE ANTIHYPERTENSIVE EFFICACY OF THE NEW RENIN INHIBITOR RO 42-5892

The objective of this study was to assess the antihypertensive efficac y of the new renin inhibitor Ro 42-5892 in patients with essential hyp ertension treated with 100 mg once daily orally. This was a double-bli nd, placebo-controlled, parallel group trial. After three weeks of was h-out and one week of single-blind placebo run-in periods, 25 patients with mild to moderate essential hypertension (sitting DBP between 95 and 114 mmHg) were randomised to receive either placebo (n = 12) or 10 0 mg of Ro 42-5892 (n = 13) once daily for eight days. On the eighth d ay, four hours after the oral administration, patients were randomised to receive intravenously either placebo or 10 mg of Ro 42-5892. BP an d heart rate were measured repeatedly (hourly for eight hours and at t he 24th hour post-dose) on the first and last days of active treatment . Compared with the placebo group, a slight decrease in sifting DBP wa s observed after the first dose in the Ro 42-5892 group. The decrease in sitting DBP reached significant levels only at six to eight hours p ost-dosing. In contrast, on the last day of active treatment, a larger , faster and longer decrease in sifting DBP was observed in the Ro 42- 5892 group. Thus, the peak effect (-8.9 +/- 1.9 vs. -2.9 +/- 1.3 mmHg, P < 0.01) was reached 1.5 hours post-dosing and the trough effect (24 hours post-dosing) was slightly but significantly lower when compared with the placebo group (-3.0 +/- 1.0 vs -0.3 +/- 0.8 mmHg, P < 0.05, respectively). Intravenous administration of Ro 42-5892 was not associ ated with significant changes in BP. No changes in heart rate were obs erved and no adverse events were reported. These observations indicate that, in the present study population, a short-term treatment with 1 00 mg of Ro 42-5892 was associated with a significant fall in BP for a t least 24 hours after eight days of treatment and that the duration o f treatment appears to be an important determinant of the efficacy of Ro 42-5892 at this dose.