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)
Aparicio
M
M
Service de Nephrologie, CHU de Rouen, France.
Dratwa
M
M
el Esper
N
N
Fillastre
J P
JP
Levaltier
B
B
Lins
R
R
Meyrier
A
A
Mignon
F
F
Ryckelynck
J P
JP
Sennesael
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D003404:Creatinine / Q000378:metabolism; D015314:Dialysis Solutions / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D000077769:Rilmenidine; D016037:Single-Blind Method
D000959:Antihypertensive Agents; D015314:Dialysis Solutions; D010080:Oxazoles; D003404:Creatinine; D000077769:Rilmenidine