Paliperidone

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H301：Giftig bei Verschlucken.

• Sicherheit

  P301+P310：BEI VERSCHLUCKEN: Sofort GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

Paliperidone Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R25:Giftig beim Verschlucken.

• S-Sätze Betriebsanweisung:

  S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).

• Beschreibung

  Paliperidone, the C-9 hydroxylated active metabolite of the antipsychotic agent risperidone, is the newest atypical antipsychotic to join the market following the introductions of olanzapine (ZyprexaTM), risperidone (RisperdalTM), quetiapine(SeroquelTM), and ziprasidone (GeodonTM). Compared to its parent, paliperidone has improved PK properties and a reduced potential for drug interactions. In terms of receptor affinity, the two drugs are equipotent.

• Chemische Eigenschaften

  Off White to Light Orange Coloured Solid

• Originator

  Johnson & Johnson (US)

• Verwenden

  A metabolite of Risperidone, a combined serotonin (5-HT2) and dopamine (D2) receptor antagonist

• Verwenden

  Paliperidone(Invega) is an atypical antipsychotic. Chemically, paliperidone is the primary active metabolite of the older atypical antipsychotic risperidone. It is indicated for the acute and maintenance treatment of schizophrenia

• Definition

  ChEBI: 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one is a member of the class of pyridopyrimidines that is 9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one carrying an additional 2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl group at position 2. It is a member of 1,2-benzoxazoles, a heteroarylpiperidine, an organofluorine compound, a pyridopyrimidine and a secondary alcohol.

• Trademarks

  Invega

• Allgemeine Beschreibung

  Paliperidone, (±)-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one(Invega), is essentially insoluble in water and is available asextended-release tablets. Paliperidone is delivered at a constantrate using an osmotic drug release device (OsmoticRelease Oral Systems [OROS]). The absolute bioavailabilityof paliperidone is 28%, and studies in healthy subjects on ahigh-fat, high-calorie meal showed an increase in AUC.Paliperidone is 74% bound to plasma proteins. After a single,1-mg dose of C-paliperidone, 59% of the dose was excretedin the urine as unchanged drug, and 32% of the dose was recoveredas metabolites. Most of the drug (80%) is excreted bythe kidneys. Paliperidone is metabolized by dealkylation, hydroxylation,dehydrogenation, and scission of the benzoxazolering. None of these metabolic pathways account for morethan 10% of the dose. The terminal elimination half-life ofpaliperidone is 23 hours.

• Biochem/physiol Actions

  Paliperidone is an atypical antipsychotic; active metabolite of risperidone.

• Nebenwirkungen

  The most common adverse events included tachycardia, QTc prolongation, headache, anxiety, dizziness, tremors, and insomnia along with the dose-related events of somnolence, orthostatic hypotension, salivary hypersecretion, and extrapyrimidal disorder. Weight gain was also observed in 6–9% of patients which may be attributable to paliperidone’s lower affinity for H1-histaminergic and a1- and a2-adrenergic receptors. Patients with renal impairment require dose adjustments since elimination of paliperidone is altered. Paliperidone is contraindicated in patients with a hypersensitivity to risperidone. Concomitant use of class III antiarrhythmic agents should be avoided since this may result in additive QT interval prolongation. Also, loss of levodopa efficacy is expected with this D2 antagonist.

• Synthese

  The synthesis of paliperidone involves the reaction of 2-acetyl-g-butyrolactone with 2-amino-3-benzyloxypyridine in the presence of phosphoryl chloride. The benzyl protecting group of the intermediate 9-benzyloxy- 3-(2-chloroethyl)-2-methylpyrido[1,2-a]pyrimidin-4-one is then removed by hydrogenolysis over Pd/C followed by the nucleophilic displacement of the chlorine with 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole to provide racemic paliperidone. While paliperidone can be resolved, both enantiomers are equipotent and interconvert in vivo obviating the need for separation.

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Anaesthetics: enhanced hypotensive effect.
  Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone.
  Anti-arrhythmics: increased risk of ventricular arrhythmias when given with anti-arrhythmics that prolong the QT interval.
  Antidepressants: increases concentration of tricyclics (possibly increased risk of ventricular arrhythmias).
  Antiepileptics: antagonise anticonvulsant effect (convulsive threshold lowered); concentration reduced by carbamazepine.
  Antimalarials: avoidance of antipsychotics advised by manufacturer of artemether/lumefantrine.
  Antipsychotics: possible increased risk of ventricular arrhythmias with risperidone.
  Antivirals: concentration possibly increased by ritonavir.
  Atomoxetine: increased risk of ventricular arrhythmias with atomoxetine.
  Cytotoxics: increased risk of ventricular arrhythmias with arsenic trioxide.

• Stoffwechsel

  Paliperidone is the active metabolite of risperidone. Four metabolic pathways have been identified in vivo, none of which accounted for more than 6.5% of the dose: dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission.
  Following administration of [14C]-paliperidone, 59% of the dose was excreted unchanged into urine, indicating that paliperidone is not extensively metabolised in the liver. Approximately 80% of the administered radioactivity was recovered in urine and 11% in the faeces.

• Lager

  +4°C

• Einzelnachweise

  1) Beijsterveldt?et al.?(1994),?Regional brain distribution of risperidone and its active metabolite 9-hydroxy-risperidone in the rat; Psychopharmacology,?114?53 DOI:10.1007/BF02245444
  2) Leysen?et al. (1994),?Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity; J. Clin. Psychiatry,?55?suppl: 5 PMID: 7520908
  3) Schotte?et al.?(1996),?Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding; Psychopharmacology (Berl.),?124?57 DOI:10.1007/BF02245606

Paliperidone Upstream-Materialien And Downstream Produkte

Paliperidone Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(548)Suppliers

144598-75-4, Paliperidone Verwandte Suche: