PHARMACOKINETICS OF IMIDAPRIL AND ITS ACTIVE METABOLITE IMIDAPRILAT FOLLOWING SINGLE-DOSE AND DURING STEADY-STATE IN PATIENTS WITH IMPAIREDLIVER-FUNCTION

Objective: The possible influence of impaired liver function on the ph armacokinetic disposition of imidapril, a novel prodrug type angiotens in-converting enzyme (ACE) inhibitor, and its active metabolite, imida prilat, was investigated. Methods: Eight subjects with normal liver fu nction and eight patients with liver dysfunction received an oral dose of 10 mg imidapril once daily for 7 days.Results: Plasma imidapril co ncentrations after single and, although less pronounced, after repeate d dosing were higher in the liver disease patients, whereas imidaprila t concentrations were lower. This suggests that the conversion of imid april into imidaprilat in the liver is delayed in patients with impair ed liver function. However, the slower biotransformation did not resul t in statistically significant differences in C-max 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 sli ghtly affected in patients with impaired liver function.