PHARMACOKINETICS AND RELATED PHARMACODYNAMICS OF ANTICHOLINERGIC DRUGS

The pharmacokinetics and some pharmacodynamic properties of atropine, glycopyrrolate and scopolamine are reviewed. With the development of new analytical methods for drug determination, it is now possible to measure relatively low concentrations of these drugs in biological fluids and, consequently, some new kinetic data have been collected. Following intravenous administration, a fast disappearance from the circulation is observed and due to a high total clearance value their elimination phase half-lives vary from 1 to 4 h. All these agents are nonselective muscarinic receptor antagonists, but their actions on various organ systems with cholinergic innervation show considerable diversity. The cardiovascular effects are of short duration; other peripheral muscarinic effects and CNS effects can last up to 8 h or even longer. Differing from atropine and scopolamine, glycopyrrolate as a quaternary amine penetrates the biological membranes (blood-CNS, placental barriers) slowly and incompletely, making it the drug of choice for elderly patients with coexisting diseases and for obstetric use. Similarly, its oral absorption is slow and erratic, and hence it cannot be used as an oral premedicant. Atropine, scopolamine and glycopyrrolate have a definitely faster absorption rate, when injected into the deltoid muscle compared with administration into the gluteal or vastus lateralis muscles. There appear to be significant differences in the metabolism and renal excretion of these agents. Scopolamine is apparently excreted into the urine mainly as inactive metabolites, nearly half of the atropine dose administered is recovered in the urine as the parent drug or as active metabolites and about 80% of glycopyrrolate is excreted as unchanged drug or active metabolites. However, despite the diversity in some pharmacokinetic features, the differences in clinical effects are not very prominent in healthy patients.