Abstract
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.
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Pharmacy and Pharmacology |
| Vol/bind | 69 |
| Udgave nummer | 9 |
| Sider (fra-til) | 1110-1115 |
| ISSN | 0022-3573 |
| DOI | |
| Status | Udgivet - sep. 2017 |