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Identification
NamePalonosetron
Accession NumberDB00377  (APRD00351)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionPalonosetron (INN, trade name Aloxi) is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy and is the only drug of its class approved for this use by the U.S. Food and Drug Administration. As of 2008, it is the most recent 5-HT3 antagonist to enter clinical use. [wikipedia]
Structure
Thumb
Synonyms
(3aS)-2-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-2,3,3a, 4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one
(3aS)-2,3,3a,4,5,6-hexahydro-2-[(3S)-3-quinuclidinyl]-1H-benz[de]isoquinolin-1-one
Palonosetron
Palonosétron
Palonosetrón
Palonosetronum
External Identifiers
  • 2-Qhbiqo
  • RS 25259
  • RS 25259-197
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AloxiInjection.075 mg/1.5mLIntravenousEisai Inc.2014-05-28Not applicableUs
AloxiCapsule, gelatin coated.5 mg/1OralEisai Inc.2008-08-22Not applicableUs
AloxiCapsule500 μgOralHelsinn Birex Pharmaceuticals Ltd.2005-03-22Not applicableEu
AloxiSolution0.25 mgIntravenousEisai Limited2012-07-19Not applicableCanada
AloxiCapsule500 μgOralHelsinn Birex Pharmaceuticals Ltd.2005-03-22Not applicableEu
AloxiCapsule0.5 mgOralEisai Limited2012-08-07Not applicableCanada
AloxiInjection.25 mg/5mLIntravenousEisai Inc.2014-05-28Not applicableUs
AloxiInjection, solution250 μgIntravenousHelsinn Birex Pharmaceuticals Ltd.2005-03-22Not applicableEu
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Palonosetron HospiraInjection, solution250 μgIntravenousHospira Uk Limited2016-04-08Not applicableEu
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
JioutingJiuyuan Gene Engineering
OnicitPfizer
PalnoxGlenmark
PaloxiKalbe
PalzenDr. Reddy's
ThemisetThemis Medicare
ZhiruoChia Tai Tianqing
Brand mixtures
NameLabellerIngredients
AkynzeoEisai Inc.
Salts
Name/CASStructureProperties
Palonosetron Hydrochloride
ThumbNot applicableDBSALT001057
Categories
UNII29WVV1OJ05
CAS number135729-56-5
WeightAverage: 296.414
Monoisotopic: 296.188863401
Chemical FormulaC19H24N2O
InChI KeyCPZBLNMUGSZIPR-NVXWUHKLSA-N
InChI
InChI=1S/C19H24N2O/c22-19-16-6-2-4-14-3-1-5-15(18(14)16)11-21(19)17-12-20-9-7-13(17)8-10-20/h2,4,6,13,15,17H,1,3,5,7-12H2/t15-,17-/m1/s1
IUPAC Name
(5S)-3-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-3-azatricyclo[7.3.1.0⁵,¹³]trideca-1(12),9(13),10-trien-2-one
SMILES
[H][C@]12CCCC3=C1C(=CC=C3)C(=O)N(C2)[C@@H]1CN2CCC1CC2
Pharmacology
IndicationFor the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy, as well as prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy. Also used for the prevention of postoperative nausea and vomiting for up to 24 hours post operation.
Structured Indications
PharmacodynamicsPalonosetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron is a highly specific and selective serotonin 5-HT3 receptor antagonist that is pharmacologically related to other 5-HT3 receptor antagonists, but differs structurally. Palonosetron has a high affinity for 5-HT3 receptors, but has little to no affinity for other receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
Mechanism of actionPalonosetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. Alternative mechanisms appear to be primarily responsible for delayed nausea and vomiting induced by emetogenic chemotherapy, since similar temporal relationships between between serotonin and emesis beyond the first day after a dose have not been established, and 5-HT3 receptor antagonists generally have not appeared to be effective alone in preventing or ameliorating delayed effects. It has been hypothesized that palonosetron's potency and long plasma half-life may contribute to its observed efficacy in preventing delayed nausea and vomiting caused by moderately emetogenic cancer chemotherapy.
TargetKindPharmacological actionActionsOrganismUniProt ID
5-hydroxytryptamine receptor 3AProteinyes
antagonist
HumanP46098 details
Related Articles
AbsorptionLow oral bioavailability.
Volume of distribution
  • 8.3 ± 2.5 L/kg
Protein binding62%
Metabolism

Hepatic (50%), primarily CYP2D6-mediated, although CYP3A4 and CYP1A2 are also involved.

Route of eliminationAfter a single intravenous dose of 10 mcg/kg [14C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine
Half lifeApproximately 40 hours
Clearance
  • 160 +/- 35 mL/h/kg
ToxicityA single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Palonosetron can be increased when it is combined with Abiraterone.Approved
AlmotriptanPalonosetron may increase the serotonergic activities of Almotriptan.Approved, Investigational
AmiodaroneThe metabolism of Palonosetron can be decreased when combined with Amiodarone.Approved, Investigational
AmitriptylinePalonosetron may increase the serotonergic activities of Amitriptyline.Approved
AmoxapinePalonosetron may increase the serotonergic activities of Amoxapine.Approved
ApomorphinePalonosetron may increase the hypotensive activities of Apomorphine.Approved, Investigational
AprepitantThe serum concentration of Palonosetron can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Palonosetron can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Palonosetron can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Palonosetron can be decreased when combined with Atomoxetine.Approved
AzithromycinThe metabolism of Palonosetron can be decreased when combined with Azithromycin.Approved
BetaxololThe metabolism of Palonosetron can be decreased when combined with Betaxolol.Approved
BexaroteneThe serum concentration of Palonosetron can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe metabolism of Palonosetron can be decreased when combined with Boceprevir.Approved
BortezomibThe metabolism of Palonosetron can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Palonosetron can be decreased when it is combined with Bosentan.Approved, Investigational
BromocriptinePalonosetron may increase the serotonergic activities of Bromocriptine.Approved, Investigational
BupropionThe metabolism of Palonosetron can be decreased when combined with Bupropion.Approved
BuspironePalonosetron may increase the serotonergic activities of Buspirone.Approved, Investigational
CabergolinePalonosetron may increase the serotonergic activities of Cabergoline.Approved
CaffeineThe metabolism of Palonosetron can be decreased when combined with Caffeine.Approved
CarbamazepineThe metabolism of Palonosetron can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Palonosetron can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Palonosetron can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Palonosetron can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Palonosetron can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Palonosetron can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Palonosetron can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Palonosetron can be decreased when combined with Cinacalcet.Approved
CitalopramPalonosetron may increase the serotonergic activities of Citalopram.Approved
ClarithromycinThe metabolism of Palonosetron can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Palonosetron can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Palonosetron can be decreased when combined with Clobazam.Approved, Illicit
ClomipraminePalonosetron may increase the serotonergic activities of Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Palonosetron can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Palonosetron can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Palonosetron can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Palonosetron can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Palonosetron can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Palonosetron can be decreased when combined with Crizotinib.Approved
CyclobenzaprinePalonosetron may increase the serotonergic activities of Cyclobenzaprine.Approved
CyclosporineThe metabolism of Palonosetron can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Cyproterone acetateThe serum concentration of Palonosetron can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Palonosetron can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Palonosetron can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Palonosetron can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Palonosetron can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Palonosetron can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Palonosetron can be decreased when combined with Delavirdine.Approved
DesipraminePalonosetron may increase the serotonergic activities of Desipramine.Approved
DesvenlafaxinePalonosetron may increase the serotonergic activities of Desvenlafaxine.Approved
DexamethasoneThe serum concentration of Palonosetron can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanPalonosetron may increase the serotonergic activities of Dextromethorphan.Approved
DihydroergotamineThe metabolism of Palonosetron can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Palonosetron can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Palonosetron can be decreased when combined with Diphenhydramine.Approved
DoxepinPalonosetron may increase the serotonergic activities of Doxepin.Approved
DoxycyclineThe metabolism of Palonosetron can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Palonosetron can be decreased when combined with Dronedarone.Approved
DuloxetinePalonosetron may increase the serotonergic activities of Duloxetine.Approved
EfavirenzThe serum concentration of Palonosetron can be decreased when it is combined with Efavirenz.Approved, Investigational
EletriptanPalonosetron may increase the serotonergic activities of Eletriptan.Approved, Investigational
EliglustatThe metabolism of Palonosetron can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Palonosetron can be decreased when it is combined with Enzalutamide.Approved
Ergoloid mesylatePalonosetron may increase the serotonergic activities of Ergoloid mesylate.Approved
ErgonovinePalonosetron may increase the serotonergic activities of Ergonovine.Approved
ErgotaminePalonosetron may increase the serotonergic activities of Ergotamine.Approved
ErythromycinThe metabolism of Palonosetron can be decreased when combined with Erythromycin.Approved, Vet Approved
EscitalopramPalonosetron may increase the serotonergic activities of Escitalopram.Approved, Investigational
Eslicarbazepine acetateThe serum concentration of Palonosetron can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Palonosetron can be decreased when it is combined with Etravirine.Approved
FentanylPalonosetron may increase the serotonergic activities of Fentanyl.Approved, Illicit, Investigational, Vet Approved
FluconazoleThe metabolism of Palonosetron can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Palonosetron can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Palonosetron can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Palonosetron can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Palonosetron can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Palonosetron can be increased when combined with Fosphenytoin.Approved
FrovatriptanPalonosetron may increase the serotonergic activities of Frovatriptan.Approved, Investigational
Fusidic AcidThe serum concentration of Palonosetron can be increased when it is combined with Fusidic Acid.Approved
HaloperidolThe metabolism of Palonosetron can be decreased when combined with Haloperidol.Approved
IdelalisibThe serum concentration of Palonosetron can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Palonosetron can be decreased when combined with Imatinib.Approved
ImipraminePalonosetron may increase the serotonergic activities of Imipramine.Approved
IndinavirThe metabolism of Palonosetron can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Palonosetron can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidPalonosetron may increase the serotonergic activities of Isocarboxazid.Approved
IsoniazidThe metabolism of Palonosetron can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Palonosetron can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Palonosetron can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Palonosetron can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Palonosetron can be decreased when combined with Ketoconazole.Approved, Investigational
LevomilnacipranPalonosetron may increase the serotonergic activities of Levomilnacipran.Approved
LidocaineThe metabolism of Palonosetron can be decreased when combined with Lidocaine.Approved, Vet Approved
LinezolidPalonosetron may increase the serotonergic activities of Linezolid.Approved, Investigational
LithiumPalonosetron may increase the serotonergic activities of Lithium.Approved
LopinavirThe metabolism of Palonosetron can be decreased when combined with Lopinavir.Approved
LorcaserinPalonosetron may increase the serotonergic activities of Lorcaserin.Approved
LovastatinThe metabolism of Palonosetron can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Palonosetron can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Palonosetron can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Palonosetron can be decreased when combined with Lumefantrine.Approved
MaprotilinePalonosetron may increase the serotonergic activities of Maprotiline.Approved
MethadonePalonosetron may increase the serotonergic activities of Methadone.Approved
MethotrimeprazineThe metabolism of Palonosetron can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Palonosetron can be decreased when combined with Metoprolol.Approved, Investigational
MexiletineThe metabolism of Palonosetron can be decreased when combined with Mexiletine.Approved
MifepristoneThe serum concentration of Palonosetron can be increased when it is combined with Mifepristone.Approved, Investigational
MilnacipranPalonosetron may increase the serotonergic activities of Milnacipran.Approved
MirabegronThe metabolism of Palonosetron can be decreased when combined with Mirabegron.Approved
MirtazapinePalonosetron may increase the serotonergic activities of Mirtazapine.Approved
MitotaneThe serum concentration of Palonosetron can be decreased when it is combined with Mitotane.Approved
MoclobemidePalonosetron may increase the serotonergic activities of Moclobemide.Approved
ModafinilThe serum concentration of Palonosetron can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe serum concentration of Palonosetron can be decreased when it is combined with Nafcillin.Approved
NaratriptanPalonosetron may increase the serotonergic activities of Naratriptan.Approved, Investigational
NefazodoneThe metabolism of Palonosetron can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Palonosetron can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Palonosetron can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Palonosetron can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Palonosetron can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Palonosetron can be decreased when combined with Nilotinib.Approved, Investigational
NortriptylinePalonosetron may increase the serotonergic activities of Nortriptyline.Approved
OlaparibThe metabolism of Palonosetron can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Palonosetron can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Palonosetron can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Palonosetron can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Palonosetron can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Palonosetron can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Palonosetron can be increased when combined with Pentobarbital.Approved, Vet Approved
PethidinePalonosetron may increase the serotonergic activities of Pethidine.Approved
PhenelzinePalonosetron may increase the serotonergic activities of Phenelzine.Approved
PhenobarbitalThe metabolism of Palonosetron can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Palonosetron can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Palonosetron can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Palonosetron can be increased when combined with Primidone.Approved, Vet Approved
ProcarbazinePalonosetron may increase the serotonergic activities of Procarbazine.Approved
PromazineThe metabolism of Palonosetron can be decreased when combined with Promazine.Approved, Vet Approved
PromethazinePalonosetron may increase the serotonergic activities of Promethazine.Approved
ProtriptylinePalonosetron may increase the serotonergic activities of Protriptyline.Approved
QuinidineThe metabolism of Palonosetron can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Palonosetron can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Palonosetron can be decreased when combined with Ranolazine.Approved, Investigational
RasagilinePalonosetron may increase the serotonergic activities of Rasagiline.Approved
RifabutinThe metabolism of Palonosetron can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Palonosetron can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Palonosetron can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Palonosetron can be decreased when combined with Ritonavir.Approved, Investigational
RizatriptanPalonosetron may increase the serotonergic activities of Rizatriptan.Approved
RolapitantThe metabolism of Palonosetron can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Palonosetron can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe metabolism of Palonosetron can be decreased when combined with Saquinavir.Approved, Investigational
SelegilinePalonosetron may increase the serotonergic activities of Selegiline.Approved, Investigational, Vet Approved
SertralinePalonosetron may increase the serotonergic activities of Sertraline.Approved
SildenafilThe metabolism of Palonosetron can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Palonosetron can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Palonosetron can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Palonosetron can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Palonosetron can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Palonosetron can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SumatriptanPalonosetron may increase the serotonergic activities of Sumatriptan.Approved, Investigational
TapentadolPalonosetron may decrease the analgesic activities of Tapentadol.Approved
Tedizolid PhosphatePalonosetron may increase the serotonergic activities of Tedizolid Phosphate.Approved
TelaprevirThe metabolism of Palonosetron can be decreased when combined with Telaprevir.Approved
TelithromycinThe metabolism of Palonosetron can be decreased when combined with Telithromycin.Approved
TenofovirThe metabolism of Palonosetron can be decreased when combined with Tenofovir.Approved, Investigational
TerbinafineThe metabolism of Palonosetron can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TeriflunomideThe serum concentration of Palonosetron can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Palonosetron can be decreased when combined with Theophylline.Approved
ThioridazineThe metabolism of Palonosetron can be decreased when combined with Thioridazine.Approved
TiclopidineThe metabolism of Palonosetron can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Palonosetron can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Palonosetron can be decreased when it is combined with Tocilizumab.Approved
TramadolPalonosetron may decrease the analgesic activities of Tramadol.Approved, Investigational
TranylcyprominePalonosetron may increase the serotonergic activities of Tranylcypromine.Approved
TrazodonePalonosetron may increase the serotonergic activities of Trazodone.Approved, Investigational
TrimipraminePalonosetron may increase the serotonergic activities of Trimipramine.Approved
VemurafenibThe serum concentration of Palonosetron can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Palonosetron can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Palonosetron can be decreased when combined with Verapamil.Approved
VilazodonePalonosetron may increase the serotonergic activities of Vilazodone.Approved
VoriconazoleThe metabolism of Palonosetron can be decreased when combined with Voriconazole.Approved, Investigational
VortioxetinePalonosetron may increase the serotonergic activities of Vortioxetine.Approved
ZiprasidoneThe metabolism of Palonosetron can be decreased when combined with Ziprasidone.Approved
ZolmitriptanPalonosetron may increase the serotonergic activities of Zolmitriptan.Approved, Investigational
Food InteractionsNot Available
References
Synthesis Reference

Pierluigi Rossetto, Peter MacDonald, Ettore Bigatti, Gaia Banfi, Dario Tentorio, “Processes for preparing palonosetron salts.” U.S. Patent US20080200681, issued August 21, 2008.

US20080200681
General References
  1. De Leon A: Palonosetron (Aloxi): a second-generation 5-HT(3) receptor antagonist for chemotherapy-induced nausea and vomiting. Proc (Bayl Univ Med Cent). 2006 Oct;19(4):413-6. [PubMed:17106506 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
  3. Rubenstein EB: Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol. 2004 May;2(5):284-9. [PubMed:16163194 ]
  4. Yang LP, Scott LJ: Palonosetron: in the prevention of nausea and vomiting. Drugs. 2009 Nov 12;69(16):2257-78. doi: 10.2165/11200980-000000000-00000. [PubMed:19852528 ]
  5. Siddiqui MA, Scott LJ: Palonosetron. Drugs. 2004;64(10):1125-32; discussion 1133-4. [PubMed:15139789 ]
  6. Eisenberg P, MacKintosh FR, Ritch P, Cornett PA, Macciocchi A: Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol. 2004 Feb;15(2):330-7. [PubMed:14760130 ]
  7. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
External Links
ATC CodesA04AA55A04AA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (185 KB)
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9899
Blood Brain Barrier+0.9953
Caco-2 permeable+0.5986
P-glycoprotein substrateSubstrate0.679
P-glycoprotein inhibitor IInhibitor0.8643
P-glycoprotein inhibitor IINon-inhibitor0.6745
Renal organic cation transporterInhibitor0.5763
CYP450 2C9 substrateNon-substrate0.83
CYP450 2D6 substrateSubstrate0.7618
CYP450 3A4 substrateSubstrate0.6446
CYP450 1A2 substrateInhibitor0.6626
CYP450 2C9 inhibitorNon-inhibitor0.541
CYP450 2D6 inhibitorNon-inhibitor0.7502
CYP450 2C19 inhibitorInhibitor0.9367
CYP450 3A4 inhibitorInhibitor0.6002
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7828
Ames testNon AMES toxic0.8664
CarcinogenicityNon-carcinogens0.9557
BiodegradationNot ready biodegradable0.9762
Rat acute toxicity2.7383 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.883
hERG inhibition (predictor II)Inhibitor0.6891
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Helsinn healthcare sa
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
CapsuleOral0.5 mg
CapsuleOral500 μg
Capsule, gelatin coatedOral.5 mg/1
InjectionIntravenous.075 mg/1.5mL
InjectionIntravenous.25 mg/5mL
Injection, solutionIntravenous250 μg
SolutionIntravenous0.25 mg
Prices
Unit descriptionCostUnit
Aloxi 0.075 mg/1.5 ml vial52.8USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5202333 Yes1995-10-132015-10-13Us
US6297375 No2000-02-222020-02-22Us
US7947724 Yes2004-07-302024-07-30Us
US7947725 Yes2004-07-302024-07-30Us
US7960424 Yes2004-07-302024-07-30Us
US8518981 Yes2004-07-302024-07-30Us
US8598218 Yes2004-07-302024-07-30Us
US8598219 Yes2004-07-302024-07-30Us
US8623826 No2010-11-182030-11-18Us
US8729094 Yes2004-07-302024-07-30Us
US8951969 No2010-11-182030-11-18Us
US9066980 Yes2004-07-302024-07-30Us
US9125905 Yes2004-07-302024-07-30Us
US9173942 Yes2004-07-302024-07-30Us
US9186357 No2010-11-182030-11-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP2.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.464 mg/mLALOGPS
logP2.72ALOGPS
logP2.55ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)7.97ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area23.55 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity88.52 m3·mol-1ChemAxon
Polarizability33.9 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as isoquinolones and derivatives. These are aromatic polycyclic compounds containing a ketone bearing isoquinoline moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoquinolines and derivatives
Sub ClassIsoquinolones and derivatives
Direct ParentIsoquinolones and derivatives
Alternative Parents
Substituents
  • Isoquinolone
  • Tetrahydroisoquinoline
  • Tetralin
  • Quinuclidine
  • Piperidine
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Amino acid or derivatives
  • Carboxylic acid derivative
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Voltage-gated potassium channel activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
Gene Name:
HTR3A
Uniprot ID:
P46098
Molecular Weight:
55279.835 Da
References
  1. Hesketh PJ: New treatment options for chemotherapy-induced nausea and vomiting. Support Care Cancer. 2004 Aug;12(8):550-4. Epub 2004 Jun 30. [PubMed:15232725 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. Grunberg SM, Koeller JM: Palonosetron: a unique 5-HT3-receptor antagonist for the prevention of chemotherapy-induced emesis. Expert Opin Pharmacother. 2003 Dec;4(12):2297-303. [PubMed:14640928 ]
  4. Rubenstein EB: Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol. 2004 May;2(5):284-9. [PubMed:16163194 ]
  5. Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S: Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer. 2003 Dec 1;98(11):2473-82. [PubMed:14635083 ]
  6. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
  7. De Leon A: Palonosetron (Aloxi): a second-generation 5-HT(3) receptor antagonist for chemotherapy-induced nausea and vomiting. Proc (Bayl Univ Med Cent). 2006 Oct;19(4):413-6. [PubMed:17106506 ]
  8. Yang LP, Scott LJ: Palonosetron: in the prevention of nausea and vomiting. Drugs. 2009 Nov 12;69(16):2257-78. doi: 10.2165/11200980-000000000-00000. [PubMed:19852528 ]
  9. Navari RM: Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Future Oncol. 2006 Oct;2(5):591-602. [PubMed:17026451 ]
  10. Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M: Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003 Oct;14(10):1570-7. [PubMed:14504060 ]
  11. Siddiqui MA, Scott LJ: Palonosetron. Drugs. 2004;64(10):1125-32; discussion 1133-4. [PubMed:15139789 ]
  12. Eisenberg P, MacKintosh FR, Ritch P, Cornett PA, Macciocchi A: Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol. 2004 Feb;15(2):330-7. [PubMed:14760130 ]
  13. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
  3. Janicki PK: Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8. Epub 2005 Sep 26. [PubMed:16192915 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Stoltz R, Parisi S, Shah A, Macciocchi A: Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37. [PubMed:15378559 ]
  2. Stoltz R, Cyong JC, Shah A, Parisi S: Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol. 2004 May;44(5):520-31. [PubMed:15102873 ]
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Drug created on June 13, 2005 07:24 / Updated on December 09, 2016 03:54