Pharmacokinetics of propranolol in healthy cats during euthyroid and hyperthyroid states

Gilbert Jacobs From the Departments of Small Animal Medicine (Jacobs, Calvert) and Physiology and Pharmacology (Ferguson), College of Veterinary Medicine, University of Georgia, Athens, GA 30602; the Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, IL 61801 (Whittem); and the Ohio State Racing Commission Laboratories, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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Ted Whittem From the Departments of Small Animal Medicine (Jacobs, Calvert) and Physiology and Pharmacology (Ferguson), College of Veterinary Medicine, University of Georgia, Athens, GA 30602; the Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, IL 61801 (Whittem); and the Ohio State Racing Commission Laboratories, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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Richard Sams From the Departments of Small Animal Medicine (Jacobs, Calvert) and Physiology and Pharmacology (Ferguson), College of Veterinary Medicine, University of Georgia, Athens, GA 30602; the Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, IL 61801 (Whittem); and the Ohio State Racing Commission Laboratories, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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Clay Calvert From the Departments of Small Animal Medicine (Jacobs, Calvert) and Physiology and Pharmacology (Ferguson), College of Veterinary Medicine, University of Georgia, Athens, GA 30602; the Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, IL 61801 (Whittem); and the Ohio State Racing Commission Laboratories, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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Duncan Ferguson From the Departments of Small Animal Medicine (Jacobs, Calvert) and Physiology and Pharmacology (Ferguson), College of Veterinary Medicine, University of Georgia, Athens, GA 30602; the Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, IL 61801 (Whittem); and the Ohio State Racing Commission Laboratories, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Sams).

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Abstract

Objective

To examine the pharmacokinetic profile of propranolol in cats before and during experimentally induced hyperthyroidism.

Animals

8 conditioned, random-source, young adult, female cats.

Procedure

Propranolol was administered IV as a single bolus and 72 hours later by mouth. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 μg/kg of body weight, SC, once daily) to induce hyperthyroidism (serum thyroxine concentration, 217 ± 17 nmol/L). Blood samples were obtained at appropriate intervals before and during hyperthyroidism and were analyzed for plasma propranolol concentration by use of high-performance liquid chromatography.

Results

In all cats, a two-compartment model best described the control and hyperthyroid intravenous data. The change in thyroid status from euthyroid to hyperthyroid caused a significant (P < 0.05), but small reduction in propranolol area under the curve (19,932 ± 7,900 min·μg/L vs 15,911 ± 1,400 min · μg/L) after IV administration. In contrast, after oral administration during the hyperthyroid state, a twofold increase (P < 0.05) in propranolol area under the curve (105,430 ± 57,600 min·μg/L vs 226,811 ± 112,000 min·μg/L) and peak serum propranolol concentration (651 ± 247 μg/L vs 1191 ± 590 μg/L) were attributed to significant (P < 0.05) increase in propranolol bioavailability caused by increased fractional absorption (57 ± 28% vs 137 ± 73%) and decreased total body clearance (58 ± 27 ml/min/kg vs 30 ± 19 ml/min/kg). Mean arrival time after oral dosing was significantly lengthened by hyperthyroidism (100 ± 38 minutes vs 157 ± 71 minutes).

Clinical Relevance

Hyperthyroidism-induced changes in propranolol pharmacokinetics may signal the need to reduce doses of propranolol when they are orally administered to hyperthyroid cats. (Am J Vet Res 1997;58:398–403)

Abstract

Objective

To examine the pharmacokinetic profile of propranolol in cats before and during experimentally induced hyperthyroidism.

Animals

8 conditioned, random-source, young adult, female cats.

Procedure

Propranolol was administered IV as a single bolus and 72 hours later by mouth. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 μg/kg of body weight, SC, once daily) to induce hyperthyroidism (serum thyroxine concentration, 217 ± 17 nmol/L). Blood samples were obtained at appropriate intervals before and during hyperthyroidism and were analyzed for plasma propranolol concentration by use of high-performance liquid chromatography.

Results

In all cats, a two-compartment model best described the control and hyperthyroid intravenous data. The change in thyroid status from euthyroid to hyperthyroid caused a significant (P < 0.05), but small reduction in propranolol area under the curve (19,932 ± 7,900 min·μg/L vs 15,911 ± 1,400 min · μg/L) after IV administration. In contrast, after oral administration during the hyperthyroid state, a twofold increase (P < 0.05) in propranolol area under the curve (105,430 ± 57,600 min·μg/L vs 226,811 ± 112,000 min·μg/L) and peak serum propranolol concentration (651 ± 247 μg/L vs 1191 ± 590 μg/L) were attributed to significant (P < 0.05) increase in propranolol bioavailability caused by increased fractional absorption (57 ± 28% vs 137 ± 73%) and decreased total body clearance (58 ± 27 ml/min/kg vs 30 ± 19 ml/min/kg). Mean arrival time after oral dosing was significantly lengthened by hyperthyroidism (100 ± 38 minutes vs 157 ± 71 minutes).

Clinical Relevance

Hyperthyroidism-induced changes in propranolol pharmacokinetics may signal the need to reduce doses of propranolol when they are orally administered to hyperthyroid cats. (Am J Vet Res 1997;58:398–403)

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