Pharmacokinetic-dynamic study on different oral biperiden formulations in volunteers

The pharmacodynamic and kinetic profiles of two oral biperiden formulations (tablet with instant-release and sugar-coated tablet with slow-release) were studied in a total of 12 healthy subjects after the administration of a 4 mg dose and compared in part to placebo. Biperiden as slow-release formulation showed much slower absorption than the instant-release tablet; whereas plasma levels peaked as early as 1-2 h after administration of the tablet, with the slow-release formulation a first peak was seen approximately 4.5 h after intake in the majority of the subjects. In some subjects this was followed by a trough, in others by formation of a shoulder at around 0.5 ng/ml. In all subjects a peak of about 1.0 ng/ml was reached after 10-12 h. The instant-release tablet and the slow-release formulation showed comparable bioavailability. Plasma concentrations for the slow-release formulation at 24 h were around 0.5 ng/ml, about twice as high as those for the instant-release formulation. The ratio of peak to 24 h values showed the marked reduction which is characteristic for a slow-release formulation compared with the instant-release tablet. The subjective well-being of the volunteers was not influenced by the slow-release formulation, whereas after the instant-release tablet slight CNS effects (dizziness, drowsiness and fatigue) were reported up to 6 h after ingestion. Furthermore, objectively quantifiable pharmacodynamic ocular parameters (near-point accomodation, pupil size) and the secretion of saliva proved to be less affected by the slow-release formulation than by the instant-release tablet, or not affected at all.