Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with chronic renal failure.
OBJECTIVE
An open study on the single dose and steady-state pharmacokinetics of imidapril, a novel prodrug-type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite imidaprilat was conducted in eight patients with moderate chronic renal failure [mean creatinine clearance (CL(CR)) 64 ml x min(-1); range 42-77 ml x min(-1)], eight patients with severe chronic renal failure (mean CL(CR), 18 ml x min(-1); range 11-29 ml x min(-1)) and eight healthy volunteers with normal renal function. Subjects received an oral dose of 10 mg imidapril once per day for 7 days.


RESULTS
No statistical differences of either maximum concentration (Cmax) or the area under the curve (AUC) were found between patients with moderate renal failure and healthy subjects. However, Cmax and AUC for both imidapril and imidaprilat were significantly higher in patients with severe renal impairment than in healthy volunteers. There were no clinically relevant differences among the three subject groups with regard to total urinary excretion of both imidapril and imidaprilat.


CONCLUSIONS
The smallest imidapril dose which is clinically effective should be used in patients with severe renal insufficiency.
Hoogkamer
J F
JF
Clin-Pharma Research AG, Center for Clinical Pharmacology, Birsfelden, Switzerland. CPRCH@DATACOMM.CH
Kleinbloesem
C H
CH
Nokhodian
A
A
Ouwerkerk
M J
MJ
Lankhaar
G
G
Ungethüm
W
W
Kirch
W
W
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D048289:Imidazolidines; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D048289:Imidazolidines; D011355:Prodrugs; C065166:imidapril; C078006:imidaprilat