Pharmacokinetics of propranolol in healthy cats during euthyroid and hyperthyroid states

Gilbert Jacobs, Ted Whittem, Richard Sams, Clay Calvert, Duncan Ferguson

Research output: Contribution to journalArticlepeer-review

Abstract

Objective - To examine the pharmacokinetic profile of propanolol 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 propanolol area under the curve (105,430 ± 57,600 min · μg/L vs 226,811 ± 112,000 min · μg/L) and peak serum propanolol concentration (651 ± 247 μg/L vs 1191 ± 590 μg/L) were attributed to significant (P < 0.05) increase in propanolol 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 propanolol pharmacokinetics may signal the need to reduce doses of propanolol when they are orally administered to hyperthyroid cats.

Original languageEnglish (US)
Pages (from-to)398-403
Number of pages6
JournalAmerican journal of veterinary research
Volume58
Issue number4
StatePublished - Apr 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • veterinary(all)

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