Advertisement

Acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs

Suwanakiet Sawangkoon DVM, MSc1, Mutsumi Miyamoto DVM, MSc2, Tomohiro Nakayama DVM, PhD3, and Robert L. Hamlin DVM, PhD4
View More View Less
  • 1 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210.
  • | 2 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210.
  • | 3 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210.
  • | 4 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210.

Abstract

Objective—To determine acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs.

Animals—14 mature healthy Beagles.

Procedure—12 dogs were anesthetized with morphine and α-chloralose. Catheters were placed in the aorta, left ventricle, and right atrium to record systemic and pulmonary pressures and determine vascular resistance and cardiac output. Electrocardiograms (leads I, aVF, and V3) were recorded to determine electrocardiographic changes. Variables were measured before and after IV injection of incremental doses of carvedilol (cumulative doses, 10, 30, 70, 150, 310, and 630 μg/kg of body weight; n = 6) or vehicle alone (6). Pharmacokinetic analysis was performed, using 2 conscious dogs given 160 mg of carvedilol/kg as a single IV injection.

Results—Heart rate and velocity of fiber shortening at zero load (Vmax) increased slightly but significantly from baseline values at doses of carvedilol ≥ 310 μg/kg and 10 μg/kg, respectively. Carvedilol did not affect systemic and pulmonary pressures or vascular resistances. Intravenous administration of approximately 150 μg of carvedilol/kg resulted in a plasma carvedilol concentration of approximately 100 ng/ml. Mean elimination halflife was 54 minutes, half-life of distribution was 3.5 minutes, and volume of distribution was 2,038 ml/kg.

Conclusions and Clinical Relevance—The therapeutic plasma concentration of carvedilol in humans is 100 ng/ml. At that plasma concentration in dogs, the reduction in afterload and positive inotropic effect that we observed would be beneficial for treating heart failure and minimizing the cardiotoxic effects of doxorubicin. (Am J Vet Res 2000;61:57–60)

Abstract

Objective—To determine acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs.

Animals—14 mature healthy Beagles.

Procedure—12 dogs were anesthetized with morphine and α-chloralose. Catheters were placed in the aorta, left ventricle, and right atrium to record systemic and pulmonary pressures and determine vascular resistance and cardiac output. Electrocardiograms (leads I, aVF, and V3) were recorded to determine electrocardiographic changes. Variables were measured before and after IV injection of incremental doses of carvedilol (cumulative doses, 10, 30, 70, 150, 310, and 630 μg/kg of body weight; n = 6) or vehicle alone (6). Pharmacokinetic analysis was performed, using 2 conscious dogs given 160 mg of carvedilol/kg as a single IV injection.

Results—Heart rate and velocity of fiber shortening at zero load (Vmax) increased slightly but significantly from baseline values at doses of carvedilol ≥ 310 μg/kg and 10 μg/kg, respectively. Carvedilol did not affect systemic and pulmonary pressures or vascular resistances. Intravenous administration of approximately 150 μg of carvedilol/kg resulted in a plasma carvedilol concentration of approximately 100 ng/ml. Mean elimination halflife was 54 minutes, half-life of distribution was 3.5 minutes, and volume of distribution was 2,038 ml/kg.

Conclusions and Clinical Relevance—The therapeutic plasma concentration of carvedilol in humans is 100 ng/ml. At that plasma concentration in dogs, the reduction in afterload and positive inotropic effect that we observed would be beneficial for treating heart failure and minimizing the cardiotoxic effects of doxorubicin. (Am J Vet Res 2000;61:57–60)