Pharmacokinetics of spirapril in renal impairment.
The pharmacokinetics of spirapril and its active diacid metabolite spiraprilat were characterized in four groups of patients categorized on the basis of their renal function. No statistically significant effects of renal impairment upon the disposition of spirapril were detected. In contrast, there were significant perturbations in the pharmacokinetics of spiraprilat: The maximum plasma concentration (Cmax) values in the severely renally impaired group were 2-3 times those in the group of patients with normal renal function whereas the corresponding area under the curve (AUC) values were 5-6 times higher. However, there was no evidence of accumulation of spiraprilat in any of the groups as determined by the pharmacokinetic parameters derived after single and multiple doses. Thus, despite the evidence of a significant influence of renal impairment upon the disposition of spiraprilat, the lack of accumulation during the translation from single to multiple doses indicates that there is a considerable margin of safety for spirapril in renal impairment.
Meredith
P A
PA
University Department of Medicine & Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland, UK.
Grass
P
P
Guitard
C
C
Elliott
H L
HL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D003404:Creatinine / Q000378:metabolism; D004656:Enalapril / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D016037:Single-Blind Method
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril; D003404:Creatinine; C076884:spiraprilat