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Pharmacokinetics of dexmedetomidine administered intravenously in isoflurane-anesthetized cats

André Escobar DVM, MS1, Bruno H. Pypendop DrMedVet, DrVetSci2, Kristine T. Siao BS3, Scott D. Stanley PhD4, and Jan E. Ilkiw BVSc, PhD5
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  • 1 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 2 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 3 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 4 K. L. Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 5 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

Abstract

Objective—To determine the pharmacokinetics of dexmedetomidine administered as a short-duration IV infusion in isoflurane-anesthetized cats.

Animals—6 healthy adult domestic female cats.

Procedures—Dexmedetomidine hydrochloride was injected IV (10 μg/kg over 5 minutes [rate, 2 μg/kg/min]) in isoflurane-anesthetized cats. Blood samples were obtained immediately prior to and at 1, 2, 5, 6, 7, 10, 15, 30, 60, 90, 120, 240, and 480 minutes following the start of the IV infusion. Collected blood samples were transferred to tubes containing EDTA, immediately placed on ice, and then centrifuged at 3,901 × g for 10 minutes at 4°C. The plasma was harvested and stored at −20°C until analyzed. Plasma dexmedetomidine concentrations were determined by means of liquid chromatography–mass spectrometry. Dexmedetomidine plasma concentration-time data were fitted to compartmental models.

Results—A 2-compartment model with input in and elimination from the central compartment best described the disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats. Weighted mean ± SEM apparent volume of distribution of the central compartment and apparent volume of distribution at steady-state were 402 ± 47 mL/kg and 1,701 ± 200 mL/kg, respectively; clearance and terminal half-life (harmonic mean ± jackknife pseudo-SD) were 6.3 ± 2.8 mL/min/kg and 198 ± 75 minutes, respectively. The area under the plasma concentration curve and maximal plasma concentration were 1,061 ± 292 min•ng/mL and 17.6 ± 1.8 ng/mL, respectively.

Conclusions and Clinical Relevance—Disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats was characterized by a moderate clearance and a long terminal half-life.

Abstract

Objective—To determine the pharmacokinetics of dexmedetomidine administered as a short-duration IV infusion in isoflurane-anesthetized cats.

Animals—6 healthy adult domestic female cats.

Procedures—Dexmedetomidine hydrochloride was injected IV (10 μg/kg over 5 minutes [rate, 2 μg/kg/min]) in isoflurane-anesthetized cats. Blood samples were obtained immediately prior to and at 1, 2, 5, 6, 7, 10, 15, 30, 60, 90, 120, 240, and 480 minutes following the start of the IV infusion. Collected blood samples were transferred to tubes containing EDTA, immediately placed on ice, and then centrifuged at 3,901 × g for 10 minutes at 4°C. The plasma was harvested and stored at −20°C until analyzed. Plasma dexmedetomidine concentrations were determined by means of liquid chromatography–mass spectrometry. Dexmedetomidine plasma concentration-time data were fitted to compartmental models.

Results—A 2-compartment model with input in and elimination from the central compartment best described the disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats. Weighted mean ± SEM apparent volume of distribution of the central compartment and apparent volume of distribution at steady-state were 402 ± 47 mL/kg and 1,701 ± 200 mL/kg, respectively; clearance and terminal half-life (harmonic mean ± jackknife pseudo-SD) were 6.3 ± 2.8 mL/min/kg and 198 ± 75 minutes, respectively. The area under the plasma concentration curve and maximal plasma concentration were 1,061 ± 292 min•ng/mL and 17.6 ± 1.8 ng/mL, respectively.

Conclusions and Clinical Relevance—Disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats was characterized by a moderate clearance and a long terminal half-life.

Contributor Notes

Dr. Escobar's present address is Department of Veterinary Clinics and Surgery, Faculdade de Ciências Agrárias e Veterinárias, São Paulo State University, Jaboticabal, SP 14884-900, Brazil.

Funded by the Center for Companion Animal Health, School of Veterinary Medicine, University of California-Davis; and the Orion Corporation.

Dr. Escobar received a research internship grant funding from the CAPES Foundation, Brazil.

Address correspondence to Dr. Pypendop (bhpypendop@ucdavis.edu).