Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous‐rate infusion in the horse

Abstract

Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra-operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration-effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic-pharmacodynamic (PK-PD) actions of GLY during and after a 2-h constant-rate intravenous infusion (4 μg/kg/h) and evaluate potential PK-PD models for cardiac stimulation in adult horses. Measurements of plasma GLY concentrations, heart and respiration rates, and frequency of bowel movements were performed in six Thoroughbred horses. The time course for GLY disposition in plasma followed a tri-exponential equation characterized by rapid disappearance of GLY from blood followed by a prolonged terminal phase. Physiological monitoring revealed significant (P < 0.01) increases in heart (>70 bpm) and respiratory rates accompanied by a marked and sustained delay in the frequency of bowel movements (1.1 ± 0.2 h [saline group] vs. 6.0 ± 2.0 h [GLY group]). Two of six horses showed signs of colic during the 8-h observation period after the end of the GLY infusion, but were treated and recovered without further complications. The relationship between plasma GLY concentration and heart rate exhibited counterclockwise hysteresis that was adequately described using an effect compartment.

The pharmacokinetics of glycopyrrolate in Standardbred horses

“…The maximum rate at which GLY can be filtered by the glomerulus is the glomerular filtration rate (GFR) multiplied by the unbound fraction of GLY in plasma. The fraction of GLY bound to plasma protein over a range of plasma drug concentrations (0.1-25 ng/mL) is 37-44% (Rumpler et al, 2013). Furthermore, estimates of the GFR can be obtained by measuring creatinine because it is filtered but neither secreted nor reabsorbed and calculating the creatinine renal clearance.…”

A Reverse Phase Stability Indicating HPLC Method Development for Estimation Assay of Benzyl Alcohol and Glycopyrrolate in Glycopyrrolate Injection

“…The anion produced by the deprotonation of the alcohol group is known as benzylate or benzyloxide. 6 BnOH is used in a wide range of cosmetic products as an aroma ingredient, a preservative, a solvent, and as a component that helps reduce viscosity. 7 Low concentrations of BnOH are used in intravenous treatments, cosmetics, and topical therapeutic approaches.…”