Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with impaired liver function.
OBJECTIVE
The possible influence of impaired liver function on the pharmacokinetic disposition of imidapril, a novel prodrug type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite, imidaprilat, was investigated.


METHODS
Eight subjects with normal liver function and eight patients with liver dysfunction received an oral dose of 10 mg imidapril once daily for 7 days.


RESULTS
Plasma imidapril concentrations after single and, although less pronounced, after repeated dosing were higher in the liver disease patients, whereas imidaprilat concentrations were lower. This suggests that the conversion of imidapril into imidaprilat in the liver is delayed in patients with impaired liver function. However, the slower biotransformation did not result in statistically significant differences in Cmax and AUC for either imidapril or its active metabolite following repeated administration. Moreover, no relevant accumulation of either imidapril or imidaprilat occurred after repeated dosing.


CONCLUSIONS
Imidapril is regarded as an ACE inhibitor of which the pharmacokinetic disposition is only slightly affected in patients with impaired liver function.
Hoogkamer
J F
JF
Clin-Pharma Research AG, Center for Clinical Pharmacology, Birsfelden, Switzerland.
Kleinbloesem
C H
CH
Nokhodian
A
A
Ouwerkerk
M J
MJ
Lankhaar
G
G
Ungethüm
W
W
Kirch
W
W
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D048289:Imidazolidines; D008107:Liver Diseases / Q000378:metabolism*; D008111:Liver Function Tests
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C065166:imidapril; C078006:imidaprilat