PHARMACOKINETICS OF PROPRANOLOL IN HEALTHY EATS DURING EUTHYROID AND HYPERTHYROID STATES

Objective-To examine the pharmacokinetic profile of propranolol in cat s before and during experimentally induced hyperthyroidism. Animals-8 conditioned, random-source, young adult, female cats. Procedure-Propra nolol was administered IV as a single bolus and 72 hours later by mout h. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 mu g/kg of body weight, SC, once daily) to induce hy perthyroidism (seru m thyroxine concentration, 217 +/- 17 nmol/L). Blood samples were obta ined al appropriate intervals before and during hyperthyroidism and we re analyzed for plasma propranolol concentration by use of high-perfor mance liquid chromatography. Results-In all cats, a two-compartment mo del best described the control and hyperthyroid intravenous data. The change in thyroid status from euthyroid to hyperthyroid caused a signi ficant (P < 0.05), but small reduction in propranolol area under the c urve (19,932 +/- 7,900 min.mu g/L vs 15,911 +/- 1,400 min.mu g/L) afte r 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.mu g/L vs 226,811 +/- 112,000 min.mu g/L) and peak serum propranolol concentration (651 +/- 247 mu g/L vs 1191 +/- 590 mu g/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 clear ance (58 +/- 27 ml/min/kg vs 30 +/- 19 ml/min/kg). Mean arrival time a fter oral dosing was significantly lengthened by hyperthyroidism (100 +/- 38 minutes vs 157 +/- 71 minutes). Clinical Relevance-Hyperthyroid ism-induced changes in propranolol pharmacokinetics may signal the nee d to reduce doses of propranolol when they are orally administered to hyperthyroid cats.