Scopolamine Other names: Hyoscine

The transdermal therapeutic system (TTS) is a novel form of drug delivery designed to achieve a continuous release of hyoscine through the intact skin to the systemic circulation for up to 72 hours.

Hyoscine is a naturally occurring belladonna alkaloid and has anticholinergic properties. It acts as a competitive antagonist to acetylchloline and other parasympathomimetic agents. Its mechanism of action in the central nervous system in preventing motion sickness has yet to be elucidated. The ability of hyosine to prevent nausea and vomiting due to motion sickness may be related to inhibition of cholinergic impulse conduction from the vestibular nucleus to the higher centers of the central nervous system, as well as from the reticular formation to the vomiting centre. Hyoscine produces classical symptoms of parasympathetic blockade.

Following scopolamine patch administration, measurement of the urinary excretion has shown the equilibrium between absorption and elimination to be reached within about 6 hours. Steady plasma concentrations of hyoscine in the range of 0.17-0.33nmol/litre are produced. Provided the system is not removed, this equilibrium is maintained and plasma hyoscine levels are within this therapeutic range for up to 72 hours.

Little data about the distribution of scopolamine is available; however the drug distributes well and reaches the central nervous system. Scopolamine seems to be bound to plasma proteins in a reversible manner.

The metabolism of scopolamine has not been fully characterised. The drug appears to be metabolised in the liver (glucoronide or sulfate conjugation).

After removal of scopolamine patch, the plasma concentration diminishes slowly to approximately one third over the following 24 hours because hyoscine in the skin continues to enter the blood stream.

Scopolamine is excreted in urine. The urinary excretion rate of free and total (free plus conjugated) scopolamine was about 0.7 and 3.8 micrograms/hour, respectively after the application of a single transdermal scopolamine system. Less than 10% of the total dose is excreted in urine as unchanged drug and its metabolites over 108 hours.

Following a single application of two transdermal scopolamine systems, the average elimination half-life of the drug (free scopolamine) was 9.5 hours.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, skin irritation, genotoxicity, carcinogenic potential and toxicity to reproduction. A marginal embryotoxic effect was seen in rabbits with scopolamine hydrobromide administered by daily intravenous injection at doses that were approximately 100 times the level achieved with transdermal systems. No adverse effects were recorded in reprotoxicity studies following IV administration in rats.