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.
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 diseasepatients, 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.