Pharmacokinetics of midazolam in sevoflurane-anesthetized cats |
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| Affiliation: | 1. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA;2. Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA;3. Department of Biological and Diagnostic Services, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA;4. Office of Information and Technology, University of Tennessee, Knoxville, TN, USA;5. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA;1. Psychology Department, University of North Georgia, Dahlonega, GA, USA;2. Veterinary Referral Surgical Practice, Roswell, GA, USA;3. Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA;1. Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA;2. Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA;1. Willows Veterinary Centre & Referral Service, Shirley, Solihull, UK;2. Department of Applied Physics/Electro-Optics, Jerusalem College of Technology, Yerushalayim, Israel;1. Anesthesiology and Pain Management, Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, 2015 SW 16th Av, P.O. Box 1000123, Gainesville, FL 32610-0123, USA;2. Department of Anesthesiology and Pain Management, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina |
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| Abstract: | ObjectiveTo estimate the pharmacokinetics of midazolam and 1-hydroxymidazolam after midazolam administration as an intravenous bolus in sevoflurane-anesthetized cats.Study designProspective pharmacokinetic study.AnimalsA group of six healthy adult, female domestic cats.MethodsAnesthesia was induced and maintained with sevoflurane. After 30 minutes of anesthetic equilibration, cats were administered midazolam (0.3 mg kg–1) over 15 seconds. Venous blood was collected at 0, 1, 2, 4, 8, 15, 30, 45, 90, 180 and 360 minutes after administration. Plasma concentrations for midazolam and 1-hydroxymidazolam were measured using high-pressure liquid chromatography. The heart rate (HR), respiratory rate (fR), rectal temperature, noninvasive mean arterial pressure (MAP) and end-tidal carbon dioxide (Pe′CO2) were recorded at 5 minute intervals. Population compartment models were fitted to the time–plasma midazolam and 1-hydroxymidazolam concentrations using nonlinear mixed effect modeling.ResultsThe pharmacokinetic model was fitted to the data from five cats, as 1-hydroxymidazolam was not detected in one cat. A five-compartment model best fitted the data. Typical values (% interindividual variability where estimated) for the volumes of distribution for midazolam (three compartments) and hydroxymidazolam (two compartments) were 117 (14), 286 (10), 705 (14), 53 (36) and 334 mL kg–1, respectively. Midazolam clearance to 1-hydroxymidazolam, midazolam fast and slow intercompartmental clearances, 1-hydroxymidazolam clearance and 1-hydroxymidazolam intercompartment clearance were 18.3, 63.5 (15), 22.1 (8), 1.7 (67) and 3.8 mL minute–1 kg–1, respectively. No significant changes in HR, MAP, fR or Pe′CO2 were observed following midazolam administration.Conclusion and clinical relevanceIn sevoflurane-anesthetized cats, a five-compartment model best fitted the midazolam pharamacokinetic profile. There was a high interindividual variability in the plasma 1-hydroxymidazolam concentrations, and this metabolite had a low clearance and persisted in the plasma for longer than the parent drug. Midazolam administration did not result in clinically significant changes in physiologic variables. |
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| Keywords: | 1-hydroxymidazolam cat anesthesia midazolam pharmacokinetics sevoflurane |
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