Oral paliperidone extended-release: chemistry, pharmacodynamics, pharmacokinetics
and metabolism, clinical efficacy, safety and tolerability.
Author(s): Citrome L.
Affiliation(s): New York Medical College, Valhalla , NY, USA. nntman@gmail.com
Publication date & source: 2012, Expert Opin Drug Metab Toxicol. , 8(7):873-88
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 12 mg/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.
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