The pharmacology and formulation of paliperidone extended release

Abstract

Paliperidone, or 9-hydroxyrisperidone (Invega^®, Janssen, Antwerp, Belgium) is the major active metabolite of the atypical antipsychotic risperidone (Risperdal^®, Janssen). It possesses a similar, though not identical, receptor pharmacology to the parent molecule. There are additional differences in terms of its predominant renal metabolism, lower protein binding and decreased inhibition of P-glycoprotein leading to decreased potential for drug–drug interactions. Paliperidone is approved as an extended release (ER) tablet based on an osmotic-controlled release oral Push–Pull™ delivery system (Oral Osmotic System, OROS^®, Alza Corporation) for the treatment of schizophrenia. The ER formulation results in decreased fluctuations in plasma drug levels and allows for once-daily administration with initial tolerability that permits treatment initiation at a clinically effective dose without the need for titration. This achieves therapeutic levels rapidly and simplifies dosing regimens, leading to potentially better adherence and improved outcome. The present review focuses on the clinical implications of the pharmacology and formulation of paliperidone ER.

Keywords::

• 9-hydroxyrisperidone
• atypical antipsychotic
• drug–drug interactions
• extended release
• osmotic-controlled release oral delivery system
• paliperidone
• schizophrenia

Financial & competing interests disclosure

P Chue has received research grants and honoraria from Janssen, Pfizer, Eli Lilly, AstraZeneca, GlaxoSmithKline, Lundbeck, Bristol-Myers Squibb, Hoffmann-La Roche, Sunovion, Mylan and Novartis. G Baker has currently received funding from SinoVeda Canada Inc. for an unrelated project. E MacKenzie is employed by Lundbeck Canada Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.