Pharmacokinetics of propranolol in healthy cats during euthyroid and hyperthyroid states.

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 i.v. as a single bolus and 72 hours later by mouth. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 micrograms/kg of body weight, s.c., 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.micrograms/L vs 15,911 +/- 1,400 min.micrograms/L) after i.v. 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.micrograms/L vs 226,811 +/- 112,000 min.micrograms/L) and peak serum propranolol concentration (651 +/- 247 micrograms/L vs 1191 +/- 590 micrograms/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.