Pharmacokinetics of vatinoxan in male neutered cats anesthetized with isoflurane

Abstract

ObjectiveTo characterize the pharmacokinetics of vatinoxan in isoflurane-anesthetized cats. Study designProspective experimental study. AnimalsA group of six adult healthy male neutered cats. MethodsCats were anesthetized using isoflurane in oxygen. Venous catheters were placed to administer the drug and sample blood. Vatinoxan, 1 mg kg–1, was administered intravenously over 5 minutes. Blood was sampled before and at various times during and up to 8 hours after vatinoxan administration. Plasma vatinoxan concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time–concentration data using population methods and nonlinear mixed effect modeling. ResultsA three-compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes (mL kg–1), the metabolic clearance and two distribution clearances (mL minute–1 kg–1) were 34 (55), 151 (35), 306 (18), 2.3 (34), 42.6 (25) and 5.6 (0), respectively. Hypotension increased the second distribution clearance to 10.6. Conclusion and clinical relevanceThe pharmacokinetics of vatinoxan in anesthetized cats were characterized by a small volume of distribution and a low clearance. An intravenous bolus of 100 μg kg–1 of vatinoxan followed by constant rate infusions of 55 μg kg–1 minute–1 for 20 minutes, then 22 μg kg–1 minute–1 for 60 minutes and finally 10 μg kg–1 minute–1 for the remainder of the infusion time is expected to maintain the plasma concentration within 90%–110% of the plasma vatinoxan concentration previously shown to attenuate the cardiovascular effects of dexmedetomidine (25 μg kg–1) in conscious cats.