Effects of quinapril on angiotensin converting enzyme and plasma renin activity as well as pharmacokinetic parameters of quinapril and its active metabolite, quinaprilat, after intravenous and oral administration to mature horses

Abstract

Angiotensin converting enzyme (ACE) inhibitors improve survival and quality of life in human patients and small animals with cardiovascular and renal disease. There is limited information regarding their effects in horses. The purpose of this study was to determine the pharmacokinetics of quinapril and its effects on ACE and renin in horses. Experimental study using healthy mature horses. Six healthy horses were administered quinapril at 120 mg i.v., 120 mg per os and 240 mg per os in a 3-way crossover design. Blood was collected for measurement of quinapril and quinaprilat concentrations using ultra-high pressure liquid chromatography with mass spectrometry. Angiotensin converting enzyme activity and renin activity were measured using a radioenzymatic assay. Noncompartmental pharmacokinetic modelling and statistical analyses were performed. No adverse effects were observed during the study period. Intravenous and oral administration significantly inhibited ACE activity. Renin concentrations increased in all groups, but this increase was not statistically significant. Following i.v. administration of quinapril, mean terminal half-life was 0.694 h and 1.734 h for quinapril and quinaprilat, respectively. The mean volume of distribution and clearance for quinapril were 0.242 l/kg bwt and 11.93 ml/kg bwt/min, respectively. Maximum concentration for quinaprilat was 145 ng/ml at 0.167 h. Bioavailability of quinapril following oral administration was <5%. Quinaprilat was detected in all horses following oral administration of quinapril; however, it was below the limit of quantification of the assay (2.5 ng/ml) for most horses in the 120 mg dosing group. These results suggest that, despite low plasma concentrations, quinapril has sufficient oral absorption to produce inhibition of ACE in healthy horses. Controlled studies in clinically affected horses are indicated. Quinapril provides a potential treatment alternative for horses with cardiovascular and renal disease.