Oral paliperidone extended-release: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability

Introduction: Paliperidone is a second-generation (atypical) antipsychotic approved for the treatment of schizophrenia in adults and in adolescents aged 12-17 years. It is also approved for the treatment of adults with schizoaffective disorder, both as a monotherapy and as adjunctive therapy to mood stabilizers and/or antidepressants. Paliperidone is the active metabolite of risperidone. Areas covered: The purpose of this review is to describe the pharmacokinetic profile of paliperidone and its clinical implications in the treatment of schizophrenia and schizoaffective disorder. Background information is also provided regarding chemistry, pharmacodynamics, clinical efficacy and safety/tolerability data. Expert opinion: The recommended dose of paliperidone extended-release (ER) in adults is 6 mg/day and no initial dose titration is required. Higher doses may provide additional benefit as well as dose-related increases in some adverse reactions. The maximum recommended dose is 12mg/day. Peak plasma concentrations are reached approximately 24 h after dosing. Pharmacokinetics are dose-proportional. Terminal half-life is approximately 23 h. Renal excretion is the major route of elimination. Although paliperidone is the active metabolite of risperidone, paliperidone's route of metabolism and elimination is quite different from that for risperidone and paliperidone ER may be preferred over risperidone when liver disease, drug-drug interactions or other alterations in metabolism render the appropriate dosing of risperidone difficult to determine for an individual patient. The use of paliperidone ER will need to be considered within the context of its cost and availability as risperidone is now a generic product.