Bioavailability of propranolol in the dog

Area of Science:

• Pharmacology
• Veterinary Medicine
• Drug Metabolism

Background:

• Propranolol is a widely used beta-blocker with established therapeutic applications.
• Understanding its pharmacokinetic profile is crucial for optimizing dosing and predicting therapeutic outcomes.
• Species-specific differences in drug metabolism necessitate pharmacokinetic evaluations in relevant animal models.

Purpose of the Study:

• To characterize the pharmacokinetics of propranolol in fasted dogs.
• To compare propranolol absorption, distribution, metabolism, and excretion (ADME) following intravenous, intraportal, and oral administration.
• To determine the extent of first-pass metabolism and overall oral bioavailability of propranolol.

Main Methods:

• Single oral, intraportal, and intravenous doses of propranolol were administered to fasted dogs.
• Plasma and tissue concentrations of propranolol were measured over time.
• Pharmacokinetic parameters including distribution volume, biological half-life, absorption efficiency, and bioavailability were calculated.

Main Results:

• Extensive tissue uptake of propranolol was observed after intravenous dosing, with a distribution volume of 11 L/kg.
• The biological half-life of propranolol was 1.5 hours but was prolonged following oral and intraportal administration.
• Oral absorption efficiency of unchanged propranolol was 71%, with 62% loss due to first-pass metabolism, resulting in 27% oral bioavailability.

Conclusions:

• Propranolol undergoes significant first-pass metabolism in dogs, substantially reducing its oral bioavailability.
• The pharmacokinetic profile suggests extensive tissue distribution and a relatively short biological half-life in this species.
• These findings are critical for understanding propranolol's disposition in dogs and informing potential therapeutic use.