Development and application of a radioreceptor assay for scopolamine.

6 beta,7 beta-Epoxy-3a(1aH,5aH)-tropanyl-(S)-tropate (scopolamine) has proved to be a very effective drug in the prevention of motion sickness, however, the drug has a small therapeutic window, a low bioavailability and a short half-life. A transdermal drug delivery system (Scopoderm TTS) was developed to circumvent these problems as well as the variability in gastric absorption. In order to study the pharmacokinetics of the drug and its glucuronide, a highly sensitive radioreceptor assay with an absolute detection limit of 15 pg scopolamine was developed. In children undergoing minor surgery, a Scopoderm TTS patch of different sizes (according to the age of the children) was applied to the retro-auricular skin. Urine samples were collected and assayed for free and conjugated scopolamine. Furthermore possible anticholinergic effects on the pupil reaction, salivation, blood pressure and heart rate were monitored. The urine excretion of free and glucuronidated scopolamine showed large intra- and interindividual variations. However, in all age groups relatively high percentages of free scopolamine were found, namely 47.5% (3-6 years), 48.3% (7-12 years) and 36.0% (13-18 years) of the sum of free plus glucuronidated scopolamine. During the application of the patch, a prolonged plateau of scopolamine excretion could be found. Although in general the patches were well tolerated, both locally and systematically, moderate anticholinergic effects were observed in patients.