Absorption; metabolism and excretion of a single oral dose of 14c-paliperidone 1mg in healthy subjects (PAL-053)

Vermeir, Marc; Boom, S; Naessens, Ineke; Talluri, Krishna; Eerdekens, Mariëlle; Hargarter, L.

doi:10.1055/s-2007-991778

Cited by 13 publications

(13 citation statements)

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“…It has been suggested that this reduction in fluctuation may be associated with a reduced side-effect burden (Ereshefsky and Macarenas, 2003). Paliperidone undergoes limited hepatic metabolism (Vermeir et al, 2005) and, as such, may provide a treatment option that minimizes the risk of hepaticrelated drug-drug or drug-disease interactions in patients where this may be a concern.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies

Emsley

Berwaerts

Eerdekens³

et al. 2008

International Clinical Psychopharmacology

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Long-term efficacy and safety of paliperidone extended-release tablets (3-12 mg/day) were evaluated in pooled data from 52-week open-label extension (OLE) phases of three 6-week, placebo-controlled, double-blind (DB) trials involving 1083 schizophrenia patients. Forty-seven percent of patients completed the OLE phase. Outcome measures included Positive and Negative Syndrome Scale and Personal and Social Performance scale scores. Improvements observed on both scales in active treatment groups during the DB phases were maintained during the OLE phase. Most commonly (> or =10% patients) reported adverse events (AEs) were insomnia, headache, and akathisia. One or more serious AEs were reported by 16% of patients; two patients had a treatment-emergent AE that resulted in death (suicide). Extrapyramidal symptom-related AEs were reported by 25% of patients. Median maximum movement disorder rating scale scores indicated no severity change during the OLE. Mean (+/-SD) increase in body weight from OLE baseline to end point was 1.1+/-5.47 kg across treatment groups and there were no clinically meaningful changes for plasma glucose, insulin or lipid levels. This analysis shows that paliperidone extended-release can maintain improvements in symptoms and functioning and is generally well tolerated for up to 52 weeks in schizophrenia patients.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies

Emsley

Berwaerts

Eerdekens³

et al. 2008

International Clinical Psychopharmacology

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“…20 -22 The terminal half-life of paliperidone is approximately 1 day and is unaffected by the formulation. 23 Furthermore, paliperidone ER, unlike risperidone, does not undergo significant hepatic metabolism, 23 which may reduce the risk of clinically significant drug-drug interactions. This is a practical concern in patients with schizophrenia, who frequently have comorbidities that require additional medications.…”

mentioning

confidence: 99%

Paliperidone Extended-Release Tablets for Prevention of Symptom Recurrence in Patients With Schizophrenia

Kramer

Simpson²,

Mačiulis³

et al. 2007

Journal of Clinical Psychopharmacology

187

120

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We evaluated the efficacy of paliperidone extended-release (ER), an investigational psychotropic agent, in delaying symptom recurrence in adult patients with schizophrenia and its safety and tolerability. In this randomized, double-blind, placebo-controlled, multicenter study, patients' symptoms were stabilized during an 8-week run-in and a 6-week stabilization phases using open-label, flexibly dosed paliperidone ER (3-15 mg once daily, starting dose = 9 mg). The primary efficacy variable was the time of first recurrence of schizophrenia symptoms, which included predefined changes in symptom scores, psychiatric hospitalization, self-injury, and suicidal or aggressive behavior during the double-blind phase (paliperidone ER or placebo treatment). Based on positive efficacy, the study was terminated at the preplanned interim analysis (43 recurrence events). The interim analysis (primary analysis) included 113 patients (mean age = 41 years; 51% men, 85% white). In the intent-to-treat group, 14 paliperidone ER-treated patients (25%) experienced a recurrence event versus 29 (53%) for placebo. Time-to-recurrence was significantly different, favoring the paliperidone ER group (P = 0.005, log-rank test): 25% quantile of time-to-recurrence was 83 days (paliperidone ER) versus 23 days (placebo). Final analyses (n = 205) were confirmatory. During initial open-label treatment with paliperidone ER, symptoms improved significantly. This improvement was maintained with continued treatment, as were functioning and quality-of-life measures. Treatment-emergent adverse events rates were similar: 35% for paliperidone ER and 40% for placebo. Paliperidone ER treatment versus placebo significantly delayed time-to-recurrence in patients with schizophrenia, maintained symptom stability and measures of functioning, and was generally well tolerated in this patient population.

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“…The pharmacokinetics and the percentage of unchanged drug recovered in urine was similar for EM and for PM. One of the four metabolites (monohydroxy-paliperidone) was detected only in EM [14].…”

Section: Pharmacokineticsmentioning

confidence: 97%

“…Five healthy males (two of which were PM, the others were EM) were given 14 C-paliperidone 1 mg orally after an overnight fasting period of at least 10 h. The four urinary metabolites identified accounted each for up to a maximum of 6.5% of the dose, whereas fecal metabolites each represented between 0.4 and 0.9% of the dose, indicating that paliperidone was hepatically metabolized to a very limited extent only. Analysis of the urine samples revealed that unchanged drug accounted for 51.4-67.5% (59.4% on average) of the dose administered.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Paliperidone-ER: first atypical antipsychotic with oral extended release formulation

Lautenschlager¹,

Heinz²

2008

Expert Review of Neurotherapeutics

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Paliperidone-extended release (ER) is an antipsychotic medication newly introduced in the USA and Europe in 2007. It is the first oral atypical antipsychotic with an extended release, which is achieved by the osmotic-controlled release oral delivery system (OROS), a well-established technology already in use for CNS drugs (e.g., methylphenidate and hydromorphone). Paliperidone was in the focus of investigations for years, as it is the major metabolite (9-hydroxyrisperidone) of the widely used atypical antipsychotic risperidone. Paliperidone-ER has demonstrated clinical efficacy, safety and good tolerability on a once-daily basis in three randomized, double-blind, placebo-controlled, 6-week-studies including patients with acute schizophrenia and one randomized, double-blind, placebo-controlled long-term study assessing recurrence of psychotic symptoms in patients with schizophrenia. Key features are predominant renal elimination, therefore low risk of interaction with other drugs, good efficacy against psychotic symptoms based on D2-receptor and 5HT2A-receptor antagonism and very low affinity for muscarinic receptors resulting in absence of anticholinergic side effects. The OROS-ER technology leads to considerably lower plasma peak levels compared with nonextended-release formulations, thus possibly reducing side effects.

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Absorption; metabolism and excretion of a single oral dose of 14c-paliperidone 1mg in healthy subjects (PAL-053)

Cited by 13 publications

References 0 publications

Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies

Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies

Paliperidone Extended-Release Tablets for Prevention of Symptom Recurrence in Patients With Schizophrenia

Paliperidone-ER: first atypical antipsychotic with oral extended release formulation

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