Efficacy of oral lipid-based formulations of apomorphine and its diester in a Parkinson's disease rat model.

OBJECTIVES: Apomorphine is used to symptomatically treat Parkinson's disease (PD). Oral delivery of apomorphine is generally limited by its short plasma half-life and a hepatic first-pass metabolism. This study was aimed at evaluating the behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations.

METHODS: The behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations was evaluated using a 6-hydroxydopamine-lesioned rat model simulating PD symptomatology. Apomorphine or dipalmitoyl apomorphine (DPA) was incorporated into different lipid-based formulations and orally administered (0.24 mmol/kg) to the PD rat model. The rotations by the rats were counted.

KEY FINDINGS: The duration of response lasted to about 2.5 h with oral apomorphine- and DPA-loaded o/w emulsion, while it was increased to 6 h when DPA was incorporated in self-emulsifying drug delivery systems compared to s.c. apomorphine (1 h). This suggests that the lipid-based formulations provide a sustained drug release allowing for a steady exposure to the brain.

CONCLUSIONS: Oral lipid-based apomorphine delivery has a potential in achieving a steady response, though at a higher dose possibly eliminating the need for frequent s.c. apomorphine administration.