title: Acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs.
abstract: OBJECTIVE
  To determine acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs.
  
  
  METHODS
  14 mature healthy Beagles.
  
  
  METHODS
  12 dogs were anesthetized with morphine and alpha-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 microg/kg of body weight; n = 6) or vehicle alone (6). Pharmacokinetic analysis was performed, using 2 conscious dogs given 160 microg 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 > or = 310 microg/kg and 10 microg/kg, respectively. Carvedilol did not affect systemic and pulmonary pressures or vascular resistances. Intravenous administration of approximately 150 microg of carvedilol/kg resulted in a plasma carvedilol concentration of approximately 100 ng/ml. Mean elimination half-life was 54 minutes, half-life of distribution was 3.5 minutes, and volume of distribution was 2,038 ml/kg.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sawangkoon
authors.forename: M
authors.initials: M
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: R L
authors.initials: RL
authors.lastname: Hamlin
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004285:Dogs / Q000502:physiology*; D004562:Electrocardiography / Q000662:veterinary; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous / Q000662:veterinary; D011412:Propanolamines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol