Acceptability of rilmenidine and long-term surveillance of plasma concentrations in hypertensive patients with renal insufficiency.

Acceptability and plasma concentrations of rilmenidine, a new antihypertensive agent mainly eliminated via the kidney, were evaluated in 17 hypertensive patients (supine diastolic blood pressure, 104 +/- 3 mmHg) with renal insufficiency (creatinine clearance, 35 +/- 4 ml.minute-1/1.73 m2; range, 12 to 58). Patients were treated for six months with rilmenidine at the dose of 1 mg in the morning or 1 mg twice daily as single-drug therapy in untreated patients, or in combination or as substitution in patients already treated. Plasma concentrations of rilmenidine were measured by gas chromatography combined with mass spectrometry at Days 0, 1, 5, 7, 9, and 11, and Months 1.5, 3, 4.5, and 6 before administration. Supine and erect blood pressure (sphygmomanometer) measurements and side effects were noted at the same times. Laboratory and electrocardiographic parameters were evaluated at Days 0 and 11, and Months 1.5 and 6. Blood pressure was effectively controlled during the trial in 12 patients (mean decrease in systolic/diastolic blood pressure of 12/8 mmHg). Five patients were removed from the trial after Month 1.5 because of a rise in blood pressure (three cases) or noncompliance (two cases). Side effects were moderate and transient (dry mouth, constipation, daytime drowsiness, mood disturbances, insomnia) never requiring treatment withdrawal. Surveillance of renal function revealed no significant mean variation. Rilmenidine plasma concentrations reached steady state the fifth day at the latest and were related to the degree of renal insufficiency. When renal function was stable (13 cases), plasma concentrations did not vary until the end of the trial. When renal function was progressive (four cases), plasma concentrations increased in parallel in two patients, without the onset of side effects, and remained stable in the other two patients. In conclusion, this study confirmed the good acceptability of rilmenidine in hypertensive patients with chronic renal insufficiency. It showed stable plasma concentrations of rilmenidine during a six-month treatment in hypertensive patients with renal insufficiency, reflecting the absence of accumulation of the drug.

Efficacy and acceptability of rilmenidine for mild to moderate systemic hypertension.

A double-blind multicenter trial compared rilmenidine with placebo in the treatment of 126 patients with mild to moderate hypertension after a 4-week placebo run-in period. Patients with mild hypertension (study 1) with mean supine diastolic blood pressure (BP) between 95 and 104 mm Hg received either rilmenidine 1 mg/day (n = 31) or placebo (n = 35) for 4 weeks. In study 2, patients with moderate hypertension (mean supine diastolic BP between 105 and 115 mm Hg) received either rilmenidine 1 mg twice a day (n = 30) or placebo twice a day (n = 30) for 4 weeks. All 61 patients taking rilmenidine completed the study; 8 of the 65 patients taking placebo were withdrawn because of an increase in BP. Rilmenidine significantly reduced mean systolic and diastolic BP compared with placebo in both studies. BP was normalized (systolic less than 160 mm Hg and diastolic less than or equal to 90 mm Hg in 61% of the patients taking rilmenidine as opposed to 23% of those taking placebo (p less than 0.001). There was no significant difference in the incidence of either dry mouth or daytime drowsiness between rilmenidine, 1 mg/day, and placebo. Dry mouth was significantly more frequent with rilmenidine, 2 mg/day, than with placebo, but this difference was transient and no longer significant at the end of the study. No unexpected adverse effects occurred. Rilmenidine as single therapy appears to be effective and well accepted in the management of mild to moderate hypertension, in particular at the 1-mg/day dose, which normalized 84% of mild hypertensive patients and did not induce any significant adverse effects compared with placebo.

Efficacy and safety of rilmenidine for arterial hypertension.

To assess the long-term acceptability and efficacy of rilmenidine (S 3341), patients with placebo-resistant hypertension (diastolic blood pressure [BP] greater than or equal to 95 mm Hg and less than 115 mm Hg) were included in an open 1-year treatment study. Eight examinations allowed treatment adaptation if diastolic BP remained greater than or equal to 90 mm Hg (monotherapy with rilmenidine, 1 or 2 mg/day, followed by the addition of a diuretic, then tritherapy). Three hundred seventeen patients, aged 58.0 +/- 0.7 years, were included. Two hundred sixty-nine were followed for 1 year and 48 withdrew from the trial without any symptom suggesting a withdrawal syndrome: 4 because of adverse effects; 6, lack of efficacy despite triple therapy; 9, intercurrent diseases; 10, noncompliance independent of adverse effects; 18, personal reasons not associated with treatment; and 1, lost to follow-up. On the 12th month, the decrease in supine systolic and diastolic BP reached 25 and 17 mm Hg with monotherapy (n = 150), 26 and 17 mm Hg with double therapy (n = 90) and 20 and 15 mm Hg with triple therapy (n = 29). BP was normalized (diastolic BP less than or equal to 90 mm Hg) on months 6 and 12 in 80 and 84% of the patients, respectively. Monotherapy was maintained in 66 and 60% of these patients, respectively, two-thirds being treated with 1 mg once daily. Adverse effects with monotherapy were mainly observed at the beginning of treatment in 3 to 8%: dry mouth, asthenia, gastralgia, palpitations, drowsiness, insomnia; other adverse effects were rare (1 to 2%).(ABSTRACT TRUNCATED AT 250 WORDS)