Pharmacokinetics of rilmenidine in patients with chronic renal insufficiency and in hemodialysis patients.
The pharmacokinetics of rilmenidine (1 mg orally) was studied in 3 groups of patients with stable chronic renal insufficiency. This was an open, single-blind study following a single administration, and after 15 days of treatment. Group 1 included 11 patients with a creatinine clearance between 15 and 80 mL/min. Group 2 included 17 patients with a creatinine clearance < 15 mL/min. Group III included 10 hemodialysis patients. In patients with chronic renal failure, total plasma clearance and renal clearance of rilmenidine decreased; terminal half-life was 30-42 hours, which is clearly longer than previous values achieved in healthy volunteers. After repeated administration (1 mg daily in group 1, 1 mg every other day in group 2, 1 mg at the end of each dialysis session in group 3), the area under the curve was significantly increased, corresponding to drug accumulation. The steady state was reached after 6 days in patients in group 1 and after 8 days in patients in group 2. The pharmacokinetics of rilmenidine was linear since the terminal elimination half-life and renal clearance were not significantly different after single and repeated administration of rilmenidine. A positive correlation was found between rilmenidine total plasma clearance and creatinine clearance, and between rilmenidine renal clearance and creatinine clearance. Mean rilmenidine hemodialysance was 85 mL/min, that is, 26% of the rilmenidine renal clearance value achieved in healthy volunteers (330 mL/min). Thus, the following dosage schedule can be proposed. In patients whose creatinine clearance ranges between 15 and 80 mL/min, a 1 mg dose every day can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)