Glycopyrrolate: pharmacokinetics and some pharmacodynamic findings

Abstract

In the present study, a sensitive and reproducible radioreceptor assay (RRA) was used to evaluate the basic pharmacokinetic properties of glycopyrrolate, a quaternary amine with peripheral antimuscarinic activity. Based on the plasma levels after a single intravenous injection, 6 micrograms/kg (n = 6), the distribution phase half-life (2.22 +/- 1.26 s.d. min) and the elimination phase half-life (0.83 +/- 0.29 h) of glycopyrrolate were short due to the low distribution volume during the elimination phase (0.64 +/- 0.29 l/kg) and to the respectively high total plasma clearance value (0.54 +/- 0.14 l/kg/h). An intramuscular injection, 8 micrograms/kg (n = 6), was followed by a fast and predictable systemic drug absorption and clinical effects (heart rate increase, dry mouth). In this group the time to maximum plasma concentration (tmax) was 27.48 +/- 6.12 min and the maximum plasma concentration (Cmax) was 3.47 +/- 1.48 micrograms/l. After oral drug intake, 4 mg (n = 6), an apparently low and variable gastrointestinal absorption was found (tmax = 300.0 +/- 197.2 min, Cmax = 0.76 +/- 0.35 microgram/l), thus indicating that the oral route of drug administration is of no value as a routine premedication. The correlation between the plasma concentration of glycopyrrolate and the drug effects appears to be variable. Because of its sensitivity, the RRA method proved to be quite useful in evaluating the kinetics of glycopyrrolate and its relationship to various clinical effects.

Prophylactic glycopyrrolate prevents bradycardia after spinal anesthesia for Cesarean section: a randomized, double-blinded, placebo-controlled prospective trial with heart rate variability correlation

“…Its vagal blockade persists for two to three hours. It crosses the placental barrier to a limited extent compared with atropine [11,12], with peak fetal concentrations about 4% of maternal concentrations following IV administration in pregnant dogs. Of note, glycopyrrolate interacted with β-agonist drugs for asthma in this trial, inducing significant tachycardia in several parturients.…”

Prophylactic glycopyrrolate reduces hypotensive responses in elderly patients during spinal anesthesia: a randomized controlled trial

“…In the present study, glycopyrrolate was administered intramuscularly 15 min before the induction of spinal anesthesia based on the heart rate response following intramuscular injection. 11,18 As a result, clinically significant tachycardia was not observed in patients receiving glycopyrrolate. Additionally, no significant difference was observed in the recorded incidence of bradycardia between the two groups.…”

“…When glycopyrrolate is administered intravenously, heart rate increases within one minute. 11 This abrupt tachycardia could be serious in elderly patients, particularly patients with cardiovascular disease. 24 On the other hand, the use of an intramuscular injection of glycopyrrolate can be an alternative approach to prevent the occurrence of abrupt tachycardia and can gradually counteract the hypotensive responses following spinal anesthesia.…”

Treatment of suspected symptomatic cholelithiasis with glycopyrrolate: A prospective, randomized clinical trial

“…Pharmacokinetic studies have shown a rapid mean distribution phase half-life (2.22G1.26 minutes), with peak plasma concentrations achieved in less than 4 minutes for intravenous administration. 8 Like the tertiary amines scopolamine and atropine, glycopyrrolate is a nonselective muscarinic antagonist. 9 Glycopyrrolate is approved by the US Food and Drug Administration for use in anesthesia and in the treatment of peptic ulcer disease.…”