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. Objective: The purpose of this study was to determine the pharmacokinetics of quinapril and its effects on ACE and renin in horses. Methods: Experimental study using healthy mature horses. Methods: 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. Results: 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. Conclusions: 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.
© 2013 EVJ Ltd.
Publication Date: 2014-01-07 PubMed ID: 24175935DOI: 10.1111/evj.12206Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study evaluates the effects of quinapril, a drug used for treating cardiovascular and kidney ailments in humans and small animals, in horses. The researchers sought to understand how this drug impacts equine health, specifically looking at its effects on the enzymes involved in regulating blood pressure and how it is processed in the body of horses.
Study Objective and Design
- The objective of the study was to understand the pharmacokinetics – how the drug moves through the body – of quinapril, and to observe its effects on angiotensin converting enzyme (ACE) and renin, two components important in blood pressure regulation, in horses.
- The study employed a 3-way crossover design, where six healthy mature horses were given quinapril in three different manners – 120mg intravenous, 120mg oral, and 240mg oral.
- The horses’ blood was then tested for quinapril and its active metabolite, quinaprilat, using ultra-high pressure liquid chromatography with mass spectrometry, a method that separates and identifies these substances.
- The blood samples were also tested for ACE and renin activity, using a method known as radioenzymatic assay.
- The researchers also undertook noncompartmental pharmacokinetic modelling and statistical analyses.
Study Results and Conclusion
- No adverse effects were noted in the horses during the study period. Both intravenous and oral administration of quinapril significantly inhibited the ACE activity, and renin concentrations also increased, although not significantly.
- In terms of pharmacokinetic parameters, the average terminal half-life (the time taken for the drug’s concentration in the body to be halved) was 0.694 hours for quinapril and 1.734 hours for quinaprilat, its active metabolite, following intravenous administration.
- The average volume of distribution (how far the drug spreads throughout the body) and clearance (how quickly the drug is eliminated from the body) for quinapril were also reported.
- After oral administration, quinaprilat was detected in all horses; however, its concentration was below the assay’s limit of quantification (the smallest amount that can be quantitively determined) in most horses in the 120mg dosing group.
- Despite low plasma concentrations, the study concluded that quinapril had enough oral absorption to inhibit ACE in healthy horses.
- The researchers suggested that further controlled studies be carried out in horses with real clinical conditions, as quinapril may serve as a potential treatment alternative for horses with cardiovascular and renal disease.
Cite This Article
APA
Davis JL, Kruger K, LaFevers DH, Barlow BM, Schirmer JM, Breuhaus BA.
(2014).
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.
Equine Vet J, 46(6), 729-733.
https://doi.org/10.1111/evj.12206 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
MeSH Terms
- Administration, Intravenous
- Administration, Oral
- Angiotensin-Converting Enzyme Inhibitors / blood
- Angiotensin-Converting Enzyme Inhibitors / metabolism
- Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
- Angiotensin-Converting Enzyme Inhibitors / pharmacology
- Animals
- Area Under Curve
- Gene Expression Regulation, Enzymologic
- Half-Life
- Horses / blood
- Horses / metabolism
- Peptidyl-Dipeptidase A / blood
- Peptidyl-Dipeptidase A / genetics
- Peptidyl-Dipeptidase A / metabolism
- Quinapril
- Renin / blood
- Tetrahydroisoquinolines / blood
- Tetrahydroisoquinolines / metabolism
- Tetrahydroisoquinolines / pharmacokinetics
- Tetrahydroisoquinolines / pharmacology
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