Characterisation of the in vivo behaviour of a controlled-release formulation of levodopa (Sinemet CR).

The gastrointestinal transit and systemic absorption of Sinemet CR (50-200) controlled-release tablets and standard Sinemet (25-100) immediate-release (IR) tablets have been studied in fasted and fed healthy human subjects. Both formulations were labelled with a gamma-emitting radionuclide and their gastric emptying, colon arrival and in vivo disintegration profiles monitored using gamma scintigraphy. The IR dosage forms were found to disperse soon after administration and to empty rapidly from both fasted and fed stomachs. Erosion of the CR system was independent of food or stomach pH. The CR tablet was observed to disintegrate fully in the gastrointestinal (GI) tract, resulting in complete release of levodopa over a 3-4 h time period. Considerable intersubject variation was found to exist for levodopa absorption. Absorption was more protracted with Sinemet CR than with standard Sinemet, due to the controlled release characteristics of the tablet matrix. There was no rapid initial absorption phase and instead, a gradual build-up in the absorption profile occurred.