Pharmacokinetics of propranolol and its metabolites in horses after intravenous or oral administration.
The pharmacokinetics characteristics of propranolol (PPL) in horses was studied by administering the drug intravenously or orally to the animals. The predominant primary pathway was ring oxidation, and 4-hydroxypropranolol glucuronide (4-OHPG) was the major metabolite in both plasma and urine. Side-chain glucuronidation and oxidation were not significant. A two-compartment model was employed for PPL followed by a one-compartment model for 4-OHPG. After oral administration, one-step absorption and two-step first pass metabolism were employed. The fraction absorbed of PPL was approximately 70% after oral administration, and the bioavailability varied among individual horses from 1 to 79% depending on the first pass metabolism. The biologic half-life (T1/2) of PPL obeys the allometric equation in some animal species including rats and horses, except for human. T 1/2 of PPL in horses was approximately 2 h.
Aramaki
S
S
Laboratory of Racing Chemistry, 1731-2 Tsuruta, Utsunomiya 320-0851, Japan. sugkarmk@air.linkclub.or.jp
Mori
M
M
Nakata
M
M
Shinohara
A
A
Koizumi
T
T
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000465:Algorithms; D000818:Animals; D001711:Biotransformation; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005470:Fluorometry; D020719:Glucuronides / Q000097:blood / Q000378:metabolism / Q000652:urine; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D020719:Glucuronides; D011433:Propranolol