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Warfarin in the dog: pharmacokinetics as related to clinical response
Authors:CAROL A NEFF-DAVIS  LLOYD E DAVIS  EDWARD L GILLETTE
Institution:Clinical Pharmacology Studies Unit and Comparative Oncology Research Program, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, U.S.A
Abstract:Warfarin was administered intravenously (i.v.) as a single dose of 1.5 mg/kg to healthy dogs and the pharmacokinetic parameters were investigated. Elimination could be described by a one-compartment open model. Values for the elimination half-life and apparent specific volume of distribution were 14.5 ± 4.1 h and 0.22 ± 0.04 litre/kg, respectively. Oral maintenance doses were calculated from the data collected following i.v. administration and administered every 12 h for a total of five doses after an initial i.v. loading dose of 1.5 mg/kg. Prothrombin times increased from a control value of 8.6 ± 0.3 sec to 55.2 ± 5.2 sec over a period of 96 h. Prothrombin time returned to control values by 62 h after withdrawal of the drug. We propose a dosage regimen of warfarin for anticoagulant therapy in the dog of 0.22 mg/kg to be given orally every 12 h. Prothrombin time should be monitored during therapy and the dose of warfarin modified according to the degree of suppression of coagulation factors desired.
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