Pharmacokinetics of Intramuscular and Intravenous Glycopyrrolate in Juvenile New Zealand White Rabbits

Abstract

Glycopyrrolate is an alternative to atropine to treat bradyarrhythmias in anesthetized rabbits; however, there are no pharmacokinetic studies in the literature. Six female New Zealand White rabbits received glycopyrrolate 0.05 mg/kg intravenously (IV) in the cephalic vein or intramuscularly (IM) in a complete crossover design. Blood was collected via jugular catheter to determine glycopyrrolate concentrations at baseline, 3, 5, 10, 20, 30, 45, 60 min and 2, 4, 6, 8, 12 and 24 h post-administration. Quantification of plasma glycopyrrolate was performed using liquid chromatography–tandem mass spectrometry. Non-compartmental analysis showed fast clearance (104.03 ± 45.55 mL/kg/min), volume of distribution at steady state of 0.75 ± 0.54 L/kg and terminal half-life of 2.49 ± 1.1 h after IV administration. Terminal half-life was 3.34 ± 1.10 h, T_max was 0.07 ± 0.01 h, and C_max was 2.96 ± 2 ng/mL for the IM route. Absolute bioavailability for the IM route was 10.07% ± 3.39%, suggesting higher doses may be needed for this route of administration. This study reports the pharmacokinetic parameters of glycopyrrolate in rabbits after IV and IM administration and may help design future evidence-based administration protocols in this species.