stiripentol 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
2480 49763-96-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • estiripentol
  • stiripentol
  • diacomit
In animal models, stiripentol antagonizes seizures induced by electric shock, pentetrazole and bicuculline. In rodent models, stiripentol appears to increase brain levels of gamma-aminobutyric acid (GABA) - the major inhibitory neurotransmitter in mammalian brain. This could occur by inhibition of synaptosomal uptake of GABA and/or inhibition of GABA transaminase. Stiripentol has also been shown to enhance GABAA receptor-mediated transmission in the immature rat hippocampus and increase the mean open-duration (but not the frequency) of GABAA receptor chloride channels by a barbiturate-like mechanism. Stiripentol potentiates the efficacy of other anticonvulsants, such as carbamazepine, sodium valproate, phenytoin, phenobarbital and many benzodiazepines, as the result of pharmacokinetic interactions. The second effect of stiripentol is mainly based on metabolic inhibition of several isoenzymes, in particular CYP450 3A4 and 2C19, involved in the hepatic metabolism of other anti-epileptic medicines.
  • Molecular weight: 234.30
  • Formula: C14H18O3
  • CLOGP: 3.21
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 38.69
  • ALOGS: -2.76
  • ROTB: 3
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
1 g O

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 213.40 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
S (Water solubility) 13 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 60 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK2,JAK3,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CB,PIK3CG,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ZAP70 47
kinase-selectivity-class BRAF,GRK2 2
pfas-class PFAS structural alert (1 = True, 0 = False) 0

Approvals:

DateAgencyCompanyOrphan
Aug. 20, 2018 FDA BIOCODEX SA
Jan. 4, 2007 EMA BIOCODEX

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Seizure 240.89 78.94 83 974 152546 90474844
Product preparation issue 173.44 78.94 29 1028 2317 90625073
Status epilepticus 128.04 78.94 32 1025 18842 90608548
Petit mal epilepsy 114.98 78.94 23 1034 4935 90622455
Off label use 94.91 78.94 87 970 1102165 89525225

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Product preparation issue 221.57 62.74 36 1098 1039 42619162
Seizure 216.71 62.74 90 1044 120471 42499730
Off label use 112.58 62.74 108 1026 638227 41981974
Multiple-drug resistance 101.73 62.74 26 1108 7296 42612905
Somnolence 97.58 62.74 55 1079 141050 42479151
Decreased appetite 69.80 62.74 50 1084 193087 42427114

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Seizure 334.85 60.04 133 1966 221052 110366148
Product preparation issue 279.65 60.04 48 2051 2731 110584469
Off label use 209.54 60.04 192 1907 1499993 109087207
Somnolence 152.67 60.04 85 2014 297364 110289836
Decreased appetite 136.98 60.04 94 2005 475752 110111448
Prescribed underdose 129.37 60.04 48 2051 65126 110522074
Multiple-drug resistance 118.76 60.04 31 2068 13204 110573996
Generalised tonic-clonic seizure 118.60 60.04 43 2056 54637 110532563
Petit mal epilepsy 114.77 60.04 27 2072 7520 110579680
Epilepsy 106.13 60.04 47 2052 100162 110487038
Status epilepticus 96.13 60.04 32 2067 31539 110555661
Hyperammonaemia 80.43 60.04 23 2076 13709 110573491
Change in seizure presentation 74.30 60.04 13 2086 821 110586379
Myoclonic epilepsy 64.69 60.04 14 2085 2677 110584523
Drug ineffective 63.56 60.04 107 1992 1520433 109066767
Seizure cluster 61.04 60.04 11 2088 822 110586378

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N03AX17 NERVOUS SYSTEM
ANTIEPILEPTICS
ANTIEPILEPTICS
Other antiepileptics
MeSH PA D000927 Anticonvulsants
MeSH PA D002491 Central Nervous System Agents
CHEBI has role CHEBI:35623 anticonvulsant

Related Drugs by ATC class:

N03AX Other antiepileptics 18 drugs
beclamidebrivaracetamcannabidiolcarisbamatecenobamatefelbamatefenfluramineganaxolonelacosamidelamotriginelevetiracetamperampanel show all 18 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Myoclonic seizure indication 37356005
Severe myoclonic epilepsy in infancy indication 230437002




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
250MG DIACOMIT BIOCODEX SA N206709 Aug. 20, 2018 RX CAPSULE ORAL July 14, 2029 TREATMENT OF SEIZURES ASSOCIATED WITH DRAVET SYNDROME (DS) IN PATIENTS TAKING CLOBAZAM WHO ARE 6 MONTHS TO LESS THAN 2 YEARS OF AGE AND WEIGHING 7 KG OR MORE
500MG DIACOMIT BIOCODEX SA N206709 Aug. 20, 2018 RX CAPSULE ORAL July 14, 2029 TREATMENT OF SEIZURES ASSOCIATED WITH DRAVET SYNDROME (DS) IN PATIENTS TAKING CLOBAZAM WHO ARE 6 MONTHS TO LESS THAN 2 YEARS OF AGE AND WEIGHING 7 KG OR MORE
250MG/PACKET DIACOMIT BIOCODEX SA N207223 Aug. 20, 2018 RX FOR SUSPENSION ORAL July 14, 2029 TREATMENT OF SEIZURES ASSOCIATED WITH DRAVET SYNDROME (DS) IN PATIENTS TAKING CLOBAZAM WHO ARE 6 MONTHS TO LESS THAN 2 YEARS OF AGE AND WEIGHING 7 KG OR MORE
500MG/PACKET DIACOMIT BIOCODEX SA N207223 Aug. 20, 2018 RX FOR SUSPENSION ORAL July 14, 2029 TREATMENT OF SEIZURES ASSOCIATED WITH DRAVET SYNDROME (DS) IN PATIENTS TAKING CLOBAZAM WHO ARE 6 MONTHS TO LESS THAN 2 YEARS OF AGE AND WEIGHING 7 KG OR MORE

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Cytochrome P450 3A4 Enzyme WOMBAT-PK
Sodium- and chloride-dependent GABA transporter 1 Transporter IC50 4.30 WOMBAT-PK
Cytochrome P450 1A2 Enzyme WOMBAT-PK
Cytochrome P450 2C19 Enzyme WOMBAT-PK

External reference:

IDSource
D05928 KEGG_DRUG
4038316 VANDF
C0075262 UMLSCUI
CHEBI:228488 CHEBI
CHEMBL1983350 ChEMBL_ID
DB09118 DRUGBANK_ID
5311454 PUBCHEM_CID
C021092 MESH_SUPPLEMENTAL_RECORD_UI
5469 IUPHAR_LIGAND_ID
3760 INN_ID
R02XOT8V8I UNII
2054968 RXNORM
132894 MMSL
23339 MMSL
d06643 MMSL
012569 NDDF
427946009 SNOMEDCT_US
428221002 SNOMEDCT_US
137767-55-6 SECONDARY_CAS_RN

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Diacomit HUMAN PRESCRIPTION DRUG LABEL 1 68418-7939 CAPSULE 250 mg ORAL NDA 30 sections
Diacomit HUMAN PRESCRIPTION DRUG LABEL 1 68418-7940 CAPSULE 500 mg ORAL NDA 30 sections
Diacomit HUMAN PRESCRIPTION DRUG LABEL 1 68418-7941 POWDER, FOR SUSPENSION 250 mg ORAL NDA 30 sections
Diacomit HUMAN PRESCRIPTION DRUG LABEL 1 68418-7942 POWDER, FOR SUSPENSION 500 mg ORAL NDA 30 sections