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A 9-year-old 21.7-kg (47.7-lb) spayed female Rottweiler was evaluated because of progressive weakness, lethargy, and diarrhea. Signs of weakness became noticeable approximately 4 weeks prior to evaluation. The dog's weakness progressively worsened, and the diarrhea had been unsuccessfully treated several times during that period. Several days prior to evaluation, the dog developed ascites. The dog was not receiving any medications other than a flea, tick, and heartworm preventative. On physical examination, bradycardia was detected and prompted echocardiographic and ECG examinations to be performed.

ECG Interpretation

An initial lead II ECG tracing revealed an underlying sinus rhythm that was conducted with

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the pharmacokinetics of carvedilol administered IV and orally and determine the dose of carvedilol required to maintain plasma concentrations associated with anticipated therapeutic efficacy when administered orally to dogs.

Animals—8 healthy dogs.

Procedures—Blood samples were collected for 24 hours after single doses of carvedilol were administered IV (175 µg/kg) or PO (1.5 mg/kg) by use of a crossover nonrandomized design. Carvedilol concentrations were detected in plasma by use of high-performance liquid chromatography. Plasma drug concentration versus time curves were subjected to noncompartmental pharmacokinetic analysis.

Results—The median peak concentration (extrapolated) of carvedilol after IV administration was 476 ng/mL (range, 203 to 1,920 ng/mL), elimination half-life (t1/2) was 282 minutes (range, 19 to 1,021 minutes), and mean residence time (MRT) was 360 minutes (range, 19 to 819 minutes). Volume of distribution at steady state was 2.0 L/kg (range, 0.7 to 4.3 L/kg). After oral administration of carvedilol, the median peak concentration was 24 µg/mL (range, 9 to 173 µg/mL), time to maximum concentration was 90 minutes (range, 60 to 180 minutes), t1/2 was 82 minutes (range, 64 to 138 minutes), and MRT was 182 minutes (range, 112 to 254 minutes). Median bioavailability after oral administration of carvedilol was 2.1% (range, 0.4% to 54%).

Conclusions and Clinical Relevance—Although results suggested a 3-hour dosing interval on the basis of MRT, pharmacodynamic studies investigating the duration of β-adrenoreceptor blockade provide a more accurate basis for determining the dosing interval of carvedilol. (Am J Vet Res 2005;66:2172–2176)

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in American Journal of Veterinary Research