P2B001 Mechanism of Action
P2B001 contains both pramipexole and rasagiline formulated using a proprietary ER coating system. While ER pramipexole formulations have been available for over a decade, P2B001 contains the first ER formulation of rasagiline and is, additionally, the first combination of both.
Pramipexole is a dopamine receptor agonist, which mimics the effects of dopamine, while rasagiline is a selective and irreversible monoamine oxidase B (MAO-B) inhibitor, minimizing the breakdown of dopamine. It is reasonable to consider that these two agents may have complementary mechanisms of action that may act synergistically and provide an enhanced anti-parkinsonian effect.
The extended release profile of pramipexole from P2B001 Extended-Release Capsules is similar to the release profile of the marketed pramipexole (Mirapex ER). The extended release profile of rasagiline from P2B001 (unlike the immediate release marketed Azilect) was formulated to be simultaneous to the pramipexole profile based on the assumption that simultaneous release will enhance the complementary mechanism of actions.
Supporting data for the synergism is seen in a mouse MPTP-toxicity model study, where combination of rasagiline and pramipexole produced greater striatal DA levels versus individual components. Further, when the extended-release dosage was mimicked, the effect was greater than when the same combination was administered as immediate-release.
- Company Data on File