title: Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.
abstract: Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated.
authors.affiliation: Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Cordoba, Spain. Electronic address: jserranor@uco.es.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Serrano-Rodríguez
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gómez-Díez
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Esgueva
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Castejón-Riber
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Cordoba, Spain; Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mena-Bravo
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Cordoba, Spain; Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain.
authors.forename: Feliciano
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, Spain.
authors.forename: Nahúm
authors.initials: N
authors.lastname: Ayala
authors.affiliation: Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Cordoba, Spain.
authors.forename: Juan Manuel Serrano
authors.initials: JMS
authors.lastname: Caballero
authors.affiliation: Equine Sport Medicine Centre, CEMEDE, University of Cordoba, Spain; Department of Medicine and Surgery, Faculty of Veterinary Medicine, University of Cordoba, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Muñoz
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001552:Benzazepines / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D018592:Cross-Over Studies; D006736:Horses / Q000097:blood* / Q000378:metabolism; D008297:Male
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; C052133:benazeprilat; C044946:benazepril
keywords: Angiotensin-converting enzyme inhibitors; Benazepril; Benazeprilat; Horses; Pharmacokinetic-pharmacodynamic