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.


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


METHODS
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).


CONCLUSIONS
Hyperthyroidism-induced changes in propranolol pharmacokinetics may signal the need to reduce doses of propranolol when they are orally administered to hyperthyroid cats.
Jacobs
G
G
Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Whittem
T
T
Sams
R
R
Calvert
C
C
Ferguson
D
D
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002371:Cat Diseases / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D002415:Cats / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D005260:Female; D006980:Hyperthyroidism / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008954:Models, Biological; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood
D000319:Adrenergic beta-Antagonists; D014284:Triiodothyronine; D011433:Propranolol; D013974:Thyroxine