Paliperidone for schizophrenia
ABSTRACT The efficacy, safety, pharmacology, pharmacokinetics, drug-drug interactions, and administration of paliperidone for schizophrenia are reviewed.
Paliperidone is a benzisoxazole derivative and the principal active metabolite of risperidone. Representative of most oxidative metabolites, paliperidone is less lipophilic than risperidone. Like other atypical antipsychotics, paliperidone has a greater affinity for serotonin type 2A- receptor blockade relative to dopamine type 2-receptor blockade. Paliperidone's advanced-generation osmotic release delivery system allows for the avoidance of dosage adjustment when initiating therapy and may decrease the frequency of antido-paminergic effects that would occur with an immediate-release formulation. The pharmacologic actions of paliperidone are similar to other high potency atypical antipsychotics. The receptor-binding profile of paliperidone most closely resembles that of risperidone and ziprasidone. Paliperidone differs from risperidone and most other antipsychotics by its relatively low extent of enzymatic metabolism. A limited number of investigations have demonstrated the ability of paliperidone to produce significant improvements in psychopathology, functioning, and relapse in patients with schizophrenia when compared with placebo. Paliperidone appears to have a similar adverse-effect profile compared to risperidone, except for an increased rate of hyperprolactinemia. The recommended dose of paliperidone for the treatment of adults with schizophrenia is 6 mg every morning.
Paliperidone does not offer any clear advantage over other atypical antipsychotics with a similar receptor-binding profile, such as risperidone and ziprasidone. Nevertheless, a few investigations have demonstrated the ability of paliperidone to produce significant improvements in psychopathology, functioning, and relapse when compared with placebo. Based on limited studies, the frequency of adverse effects, except for hyperprolactinemia, appears to favor paliperidone over risperidone.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Many patients with schizophrenia receive long-term treatment with antipsychotic medication. Switching of antipsychotic medication due to lack of efficacy, tolerability issues, and partial/non-adherence is common. Despite this, consensus strategies for switching between antipsychotics are lacking. This manuscript provides practical recommendations for switching antipsychotic medication to ensure optimal management of patients with schizophrenia, with a particular focus on paliperidone extended release (ER). The authors drew on their clinical experience supported by detailed discussion of literature describing antipsychotic switching techniques and strategies and findings from paliperidone ER clinical trials. Antipsychotic switching strategies should be individualized and take into consideration the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the pre- and post-switch medication. The use of temporary concomitant medications may be appropriate in some scenarios. Abrupt withdrawal of pre-switch medication may be appropriate in some instances but carries a greater risk of rebound and withdrawal symptoms than other strategies. Cross-tapering is the method most widely used in clinical practice. Paliperidone ER can be initiated without dose titration. The EU SmPC recommended dose of paliperidone ER is 6 mg/day; but doses should be individualized within the approved range of 3-12 mg/day. Higher doses may be required due to insufficient efficacy of the previous antipsychotic or in patients with acute symptoms. Recently diagnosed patients, those with renal impairment, or patients who have previously experienced tolerability issues with other antipsychotics may require lower doses. When switching from risperidone, higher doses of paliperidone ER may be required compared with risperidone. When switching from antipsychotics that have sedative and/or significant anticholinergic activity, the pre-switch antipsychotic should be tapered off gradually. Antipsychotics with less sedating and little anticholinergic activity can be tapered off over a shorter period. Temporary concomitant sedative medication may be beneficial when switching from antipsychotics with relatively higher sedative propensities. Switching from another antipsychotic to paliperidone ER requires individualized switching strategies and dosing, dependent on the characteristics of the patient and the PK and PD properties of the pre-switch medication. Cross-tapering strategies should be considered as a means of reducing the risk of rebound and withdrawal symptoms.Annals of General Psychiatry 04/2014; 13(1):10. DOI:10.1186/1744-859X-13-10 · 1.53 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The pharmaceutical cocrystal approach can be used to modify the properties of paliperidone. We report here two novel cocrystals, paliperidone 4-hydroxybenzoic acid cocrystal (1, 1:1, w/w) and paliperidone 4-aminobenzoic acid cocrystal (2, 1:1, w/w), with CCDC numbers of 855981 and 948923, which were constructed using paliperidone with 4-hydroxybenzoic acid and 4-aminobenzoic acid, respectively. The experimental results of the dissolution studies revealed that both 1 and 2 showed much faster dissolution rates than the original active pharmaceutical ingredient (API) in simulated gastric fluid media (pH = 1.2). The pharmacokinetic (PK) studies of 1, 2 and the original API were conducted using beagle dogs. 1 has a slightly higher maximal serum concentration, and both of the cocrystals presented considerably faster absorption rates after a single-dose oral administration to beagle dogs compared to the original API. Observed improvements suggested their potential application to the treatment of acute schizophrenia.CrystEngComm 07/2014; 16(33). DOI:10.1039/C4CE00784K · 3.86 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Paliperidone is a new antipsychotic drug with a relatively low therapeutic concentration of 20–60 ng mL−1. We established an accurate and sensitive capillary electrophoresis method for the determination of paliperidone concentrations in human plasma in this study. To minimize matrix effect caused quantification errors, paliperidone was extracted from human plasma using Oasis HLB solid phase extraction cartridges with three step washing procedure. To achieve sensitive quantification of paliperidone in human plasma, a high conductivity sample solution with sweeping-MEKC method was applied for analysis. The separation is performed in a background electrolyte composed of 75 mM phosphoric acid, 100 mM sodium dodecyl sulfate, 12% acetonitrile, and 15% tetrahydrofuran. Sample solution consisted of 10% methanol in 250 mM phosphoric acid and the conductivity ratio between sample matrix and BGE was 2.0 (γ, sample/BGE). The results showed it able to detect paliperidone in plasma samples at concentration as low as 10 ng mL−1 (S/N = 3) with a linear range between 20–200 ng mL−1. Compared to the conventional MEKC method, the sensitivity enhancement factor (SEF) of the developed sweeping-MEKC method was 100. Intra- and interday precision of peak area ratios were less than 6.03%; the method accuracy was between 93.4 and 97.9%. This method was successfully applied to the analysis of plasma samples of patients undergoing paliperidone treatment.This article is protected by copyright. All rights reservedElectrophoresis 11/2014; DOI:10.1002/elps.201400230 · 3.16 Impact Factor