title: Pharmacokinetics and pharmacodynamics of ramipril and ramiprilat in healthy cats.
abstract: The pharmacokinetics of ramipril and its active metabolite, ramiprilat, was determined in cats following single and repeated oral doses of ramipril (Vasotop tablets) (once daily for 9 days) at dose rates of 0.125, 0.25, 0.5 and 1.0 mg/kg. The pharmacodynamic effects were assessed by measuring plasma angiotensin-converting enzyme (ACE) activity. Maximum ramipril concentrations were attained within 30 min following a single dose and declined rapidly (concentrations were below the limit of quantification 4 h after treatment). Peak ramiprilat concentrations were detected at approximately 1.5 h. The apparent terminal half-life (t((1/2)beta)) was > or =20 h irrespective of the dose. Ramiprilat accumulated in plasma (ratio of accumulation 1.3 to 1.9 depending on the dose rate) following repeated administration. Steady-state conditions were attained after the second dose. Excretion was predominant in faeces (87%) and to a lesser extent in urine (11%). The rate and extent of absorption of ramipril as well as its conversion to ramiprilat were not significantly influenced by the presence of food in the gastrointestinal tract. Plasma-ACE activity was almost completely abolished 0.5-2.0 h after treatment, irrespective of the dose rate. Significant inhibition of ACE activity of 54.7 to 82.6% (depending on the dosage) was still present 24 h after treatment. Treatment was well-tolerated in all cats. Ramipril at a dose rate of 0.125 mg/kg once daily produces significant and long-lasting inhibition of ACE activity in healthy cats. The appropriateness of this dosage regime needs to be confirmed in diseased cats.
authors.affiliation: Intervet Pharma R&D, Angers Technopole, Rue Olivier de Serres, Beaucouzé Cedex, France.
authors.forename: P O
authors.initials: PO
authors.lastname: Desmoulins
authors.forename: S
authors.initials: S
authors.lastname: Burgaud
authors.forename: L J I
authors.initials: LJ
authors.lastname: Horspool
mesh_terms: D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D017257:Ramipril / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D012016:Reference Values
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C052549:ramiprilat; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril