Paliperidone palmitate

Paliperidone palmitate (PP), sold under the brand name Invega Sustenna among others, is an atypical antipsychotic which is used in the treatment of schizophrenia and schizoaffective disorder.[1][4][5] It is an antipsychotic ester – specifically the palmitate ester of paliperidone – and acts as a long-lasting form of paliperidone.[5] Paliperidone palmitate is formulated as an aqueous suspension and is administered by intramuscular injection into deltoid or gluteal muscle once every 1 or 3 months depending on the formulation.[5][6][4] A formulation for injection once every 6 months is also pending regulatory approval as of September 2021.[4][7]

Paliperidone palmitate
Clinical data
Trade namesInvega Hayfera, Invega Sustenna, Invega Trinza, others
Other namesPP; PP1M; PP3M; PP6M; JNS-010; RO-92670; RO92670
MedlinePlusa607005
License data
Routes of
administration		Intramuscular
Drug classAtypical antipsychotic
Legal status
Legal status
Identifiers
IUPAC name
  • [3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl] hexadecanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.208.402
Chemical and physical data
FormulaC39H57FN4O4
Molar mass664.907 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCCCCCCCCCCCC(=O)OC1CCCN2C1=NC(=C(C2=O)CCN3CCC(CC3)C4=NOC5=C4C=CC(=C5)F)C
InChI
  • InChI=1S/C39H57FN4O4/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-18-36(45)47-34-17-16-24-44-38(34)41-29(2)32(39(44)46)23-27-43-25-21-30(22-26-43)37-33-20-19-31(40)28-35(33)48-42-37/h19-20,28,30,34H,3-18,21-27H2,1-2H3
  • Key:VOMKSBFLAZZBOW-UHFFFAOYSA-N

With the once-monthly formulation of paliperidone palmitate, the time to peak is 13 days and the elimination half-life is 25 to 49 days, and with the 3-month formulation, the time to peak is 30 to 33 days and the half-life is 84 to 95 days via deltoid muscle and 118 to 139 days gluteally.[8] The peak-to-trough ratio of paliperidone palmitate at steady state ranges from 1.56 to 1.70 with the 1- and 3-month formulations.[8] The 3-month formulation of paliperidone palmitate has larger crystal sizes than the 1-month formulation and this allows for its longer duration.[9] No pharmacokinetic data for the 6-month formulation has been released as of January 2021.[9]

Pharmacokinetics of long-acting injectable antipsychotics
MedicationBrand nameClassVehicleDosageTmaxt1/2 singlet1/2 multiplelogPcRef
Aripiprazole lauroxilAristadaAtypicalWatera441–1064 mg/4–8 weeks24–35 days ?54–57 days7.9–10.0
Aripiprazole monohydrateAbilify MaintenaAtypicalWatera300–400 mg/4 weeks7 days ?30–47 days4.9–5.2
Bromperidol decanoateImpromen DecanoasTypicalSesame oil40–300 mg/4 weeks3–9 days ?21–25 days7.9[10]
Clopentixol decanoateSordinol DepotTypicalViscoleob50–600 mg/1–4 weeks4–7 days ?19 days9.0[11]
Flupentixol decanoateDepixolTypicalViscoleob10–200 mg/2–4 weeks4–10 days8 days17 days7.2–9.2[11][12]
Fluphenazine decanoateProlixin DecanoateTypicalSesame oil12.5–100 mg/2–5 weeks1–2 days1–10 days14–100 days7.2–9.0[13][14][15]
Fluphenazine enanthateProlixin EnanthateTypicalSesame oil12.5–100 mg/1–4 weeks2–3 days4 days ?6.4–7.4[14]
FluspirileneImap, RedeptinTypicalWatera2–12 mg/1 week1–8 days7 days ?5.2–5.8[16]
Haloperidol decanoateHaldol DecanoateTypicalSesame oil20–400 mg/2–4 weeks3–9 days18–21 days7.2–7.9[17][18]
Olanzapine pamoateZyprexa RelprevvAtypicalWatera150–405 mg/2–4 weeks7 days ?30 days–
Oxyprothepin decanoateMeclopinTypical ? ? ? ? ?8.5–8.7
Paliperidone palmitateInvega SustennaAtypicalWatera39–819 mg/4–12 weeks13–33 days25–139 days ?8.1–10.1
Perphenazine decanoateTrilafon DekanoatTypicalSesame oil50–200 mg/2–4 weeks ? ?27 days8.9
Perphenazine enanthateTrilafon EnanthateTypicalSesame oil25–200 mg/2 weeks2–3 days ?4–7 days6.4–7.2[19]
Pipotiazine palmitatePiportil LongumTypicalViscoleob25–400 mg/4 weeks9–10 days ?14–21 days8.5–11.6[12]
Pipotiazine undecylenatePiportil MediumTypicalSesame oil100–200 mg/2 weeks ? ? ?8.4
RisperidoneRisperdal ConstaAtypicalMicrospheres12.5–75 mg/2 weeks21 days ?3–6 days–
Zuclopentixol acetateClopixol AcuphaseTypicalViscoleob50–200 mg/1–3 days1–2 days1–2 days4.7–4.9
Zuclopentixol decanoateClopixol DepotTypicalViscoleob50–800 mg/2–4 weeks4–9 days ?11–21 days7.5–9.0
Note: All by intramuscular injection. Footnotes: a = Microcrystalline or nanocrystalline aqueous suspension. b = Low-viscosity vegetable oil (specifically fractionated coconut oil with medium-chain triglycerides). c = Predicted, from PubChem and DrugBank. Sources: Main: See template.

References
  1. "Invega Sustenna- paliperidone palmitate injection". DailyMed. 31 January 2019. Retrieved 19 August 2020.
  2. "Invega Trinza- paliperidone palmitate injection, suspension, extended release". DailyMed. 31 January 2019. Retrieved 19 August 2020.
  3. "Invega Hafyera- paliperidone palmitate injection, suspension, extended release". DailyMed. Retrieved 31 October 2021.
  4. "Paliperidone palmitate - Johnson & Johnson - AdisInsight".
  5. Chue P, Chue J (December 2012). "A review of paliperidone palmitate". Expert Rev Neurother. 12 (12): 1383–97. doi:10.1586/ern.12.137. PMID 23237346. S2CID 36437470.
  6. Edinoff AN, Doppalapudi PK, Orellana C, Ochoa C, Patti S, Ghaffar Y, Cornett EM, Kaye AJ, Viswanath O, Urits I, Kaye AM, Kaye AD (2021). "Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review". Front Psychiatry. 12: 699748. doi:10.3389/fpsyt.2021.699748. PMC 8490677. PMID 34621193.
  7. Peitl, Vjekoslav; Vlahović, Darko (1 June 2021). "Paliperidone Palmitate 6-month (PP6M)". Archives of Psychiatry Research. 57 (2): 229–232. doi:10.20471/dec.2021.57.02.13. eISSN 2671-2008. ISSN 2671-1079. S2CID 236334797.
  8. Correll CU, Kim E, Sliwa JK, Hamm W, Gopal S, Mathews M, Venkatasubramanian R, Saklad SR (January 2021). "Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview". CNS Drugs. 35 (1): 39–59. doi:10.1007/s40263-020-00779-5. PMC 7873121. PMID 33507525.
  9. Schoretsanitis G, Baumann P, Conca A, Dietmaier O, Giupponi G, Gründer G, Hahn M, Hart X, Havemann-Reinecke U, Hefner G, Kuzin M, Mössner R, Piacentino D, Steimer W, Zernig G, Hiemke C (February 2021). "Therapeutic Drug Monitoring of Long-Acting Injectable Antipsychotic Drugs". Ther Drug Monit. 43 (1): 79–102. doi:10.1097/FTD.0000000000000830. PMID 33196621. S2CID 226988084.
  10. Parent M, Toussaint C, Gilson H (1983). "Long-term treatment of chronic psychotics with bromperidol decanoate: clinical and pharmacokinetic evaluation". Current Therapeutic Research. 34 (1): 1–6.
  11. Jørgensen A, Overø KF (1980). "Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. III. Serum levels". Acta Psychiatrica Scandinavica. Supplementum. 279: 41–54. doi:10.1111/j.1600-0447.1980.tb07082.x. PMID 6931472.
  12. Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
  13. Ereshefsky L, Saklad SR, Jann MW, Davis CM, Richards A, Seidel DR (May 1984). "Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches". The Journal of Clinical Psychiatry. 45 (5 Pt 2): 50–9. PMID 6143748.
  14. Curry SH, Whelpton R, de Schepper PJ, Vranckx S, Schiff AA (April 1979). "Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man". British Journal of Clinical Pharmacology. 7 (4): 325–31. doi:10.1111/j.1365-2125.1979.tb00941.x. PMC 1429660. PMID 444352.
  15. Young D, Ereshefsky L, Saklad SR, Jann MW, Garcia N (1984). Explaining the pharmacokinetics of fluphenazine through computer simulations. (Abstract.). 19th Annual Midyear Clinical Meeting of the American Society of Hospital Pharmacists. Dallas, Texas.
  16. Janssen PA, Niemegeers CJ, Schellekens KH, Lenaerts FM, Verbruggen FJ, van Nueten JM, et al. (November 1970). "The pharmacology of fluspirilene (R 6218), a potent, long-acting and injectable neuroleptic drug". Arzneimittel-Forschung. 20 (11): 1689–98. PMID 4992598.
  17. Beresford R, Ward A (January 1987). "Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis". Drugs. 33 (1): 31–49. doi:10.2165/00003495-198733010-00002. PMID 3545764.
  18. Reyntigens AJ, Heykants JJ, Woestenborghs RJ, Gelders YG, Aerts TJ (1982). "Pharmacokinetics of haloperidol decanoate. A 2-year follow-up". International Pharmacopsychiatry. 17 (4): 238–46. doi:10.1159/000468580. PMID 7185768.
  19. Larsson M, Axelsson R, Forsman A (1984). "On the pharmacokinetics of perphenazine: a clinical study of perphenazine enanthate and decanoate". Current Therapeutic Research. 36 (6): 1071–88.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.