Glycopyrrolate: pharmacokinetics and some pharmacodynamic findings.

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.