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.