title: Pharmacokinetics and pharmacodynamics of ramipril and ramiprilat after intravenous and oral doses of ramipril in healthy horses.
abstract: The pharmacokinetics and pharmacodynamics (PK/PD) of the angiotensin-converting enzyme inhibitor (ACEI) ramiprilat after intravenous (IV) and oral (PO) administration of ramipril have not been evaluated in horses. This study was designed to establish PK profiles for ramipril and ramiprilat as well as to determine the effects of ramiprilat on serum angiotensin converting enzyme (ACE) and to select the most appropriate ramipril dose that suppresses ACE activity. Six healthy horses in a cross-over design received IV ramipril 0.050 mg/kg, PO at a dose of 0 (placebo), and 0.050, 0.10, 0.20, 0.40 and 0.80 mg/kg ramipril. Blood pressures were measured and blood samples obtained at different times. Serum ramipril and ramiprilat concentrations and serum ACE activity were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of ramiprilat after PO ramipril was 6-9%. Percentages of maximum ACE inhibitions from baseline were 98.88 (IV ramipril), 5.31 (placebo) and 27.68, 39.27, 46.67, 76.13 and 84.27 (the five doses of PO ramipril). Blood pressure did not change during the experiments. Although oral availability of ramiprilat was low, ramipril has sufficient enteral absorption and bioconversion to ramiprilat to induce serum ACE inhibitions of almost 85% after a dose of 0.80 mg/kg ramipril. Additional research on ramipril administration in equine patients is indicated.
authors.affiliation: Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Cordoba, Córdoba, Spain. Electronic address: jserranor@uco.es.
authors.forename: J M
authors.initials: JM
authors.lastname: Serrano-Rodríguez
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Córdoba, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gómez-Díez
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Córdoba, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Esgueva
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Córdoba, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Castejón-Riber
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Cordoba, Córdoba, Spain; Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Mena-Bravo
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Cordoba, Córdoba, Spain; Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Priego-Capote
authors.affiliation: Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Cordoba, Córdoba, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Serrano Caballero
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Córdoba, Spain; Department of Medicine and Surgery, Faculty of Veterinary Medicine, University of Cordoba, Córdoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Muñoz
mesh_terms: D061605:Administration, Intravenous / Q000662:veterinary; D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006736:Horses / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017257:Ramipril / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; C052549:ramiprilat; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril
keywords: Angiotensin-converting enzyme inhibitors; Horses; Pharmacokinetic–pharmacodynamic; Ramipril; Ramiprilat