Details of the Drug

General Information of Drug (ID: DM20VSK)

Drug Name
Istradefylline
Synonyms
KW 6002; Istradefylline [USAN:INN]; Istradefylline (JAN/USAN/INN); (E)-8-(3,4-Dimethoxystyryl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione; (E)-8-(3,4-Dimethoxystyryl)-1,3-diethyl-7-methylxanthine; 8-((1E)-2-(3,4-Dimethoxyphenyl)ethenyl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione; 8-(2-(3,4-dimethoxyphenyl)ethenyl)-1,3-diethyl-3,7-dihydro-7-methyl-1H-purine-2,6-dione; 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione
Indication
Disease Entry ICD 11 Status REF
Parkinson disease 8A00.0 Approved [1]
Substance use disorder 6C4Z Phase 1 [2]
ATC Code
N04CX01: Istradefylline
N04CX: Other antiparkinson drugs
N04C: OTHER ANTIPARKINSON DRUGS
N04: ANTI-PARKINSON DRUGS
N: NERVOUS SYSTEM
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 384.4
Logarithm of the Partition Coefficient (xlogp) 2.5
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 11,100 mcgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 181.1 mcg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2 h [3]
Clearance
The clearance of drug is 4.1-6.0 L/h [3]
Elimination
A 3mg/kg oral dose given to male rats was 17.6% elminated in the urine and 68.3% eliminated in the feces [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 64 - 69 hours [3]
Metabolism
The drug is metabolized via the CYP1A1, CYP3A4, and CYP3A5 [3]
Vd
The volume of distribution (Vd) of drug is 448-557 L [3]
Chemical Identifiers
Formula
C20H24N4O4
IUPAC Name
8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione
Canonical SMILES
CCN1C2=C(C(=O)N(C1=O)CC)N(C(=N2)/C=C/C3=CC(=C(C=C3)OC)OC)C
InChI
InChI=1S/C20H24N4O4/c1-6-23-18-17(19(25)24(7-2)20(23)26)22(3)16(21-18)11-9-13-8-10-14(27-4)15(12-13)28-5/h8-12H,6-7H2,1-5H3/b11-9+
InChIKey
IQVRBWUUXZMOPW-PKNBQFBNSA-N
Cross-matching ID
PubChem CID
5311037
ChEBI ID
CHEMBL431770
CAS Number
155270-99-8
UNII
2GZ0LIK7T4
DrugBank ID
DB11757
TTD ID
D0F4ZY
VARIDT ID
DR00611
INTEDE ID
DR0892
ACDINA ID
D01185
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Adenosine A2a receptor (ADORA2A) TTM2AOE AA2AR_HUMAN Modulator [1]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [5]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [5]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [5]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [5]
Cytochrome P450 3A5 (CYP3A5)
Main DME 		DEIBDNY CP3A5_HUMAN Substrate [5]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [5]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [5]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Substrate [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Istradefylline (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Arn-509 DMT81LZ Major Increased metabolism of Istradefylline caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [6]
Gilteritinib DMTI0ZO Moderate Decreased metabolism of Istradefylline caused by Gilteritinib mediated inhibition of CYP450 enzyme. Acute myeloid leukaemia [2A60] [7]
Troleandomycin DMUZNIG Major Decreased metabolism of Istradefylline caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [6]
MK-8228 DMOB58Q Moderate Decreased metabolism of Istradefylline caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [6]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Istradefylline caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [6]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Istradefylline caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [8]
PF-06463922 DMKM7EW Moderate Increased metabolism of Istradefylline caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [6]
Selpercatinib DMZR15V Moderate Decreased metabolism of Istradefylline caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [7]
IPI-145 DMWA24P Moderate Decreased metabolism of Istradefylline caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [6]
Rimegepant DMHOAUG Moderate Decreased clearance of Istradefylline due to the transporter inhibition by Rimegepant. Migraine [8A80] [9]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Istradefylline caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [6]
Abametapir DM2RX0I Moderate Decreased metabolism of Istradefylline caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [10]
Lefamulin DME6G97 Moderate Decreased clearance of Istradefylline due to the transporter inhibition by Lefamulin. Pneumonia [CA40] [11]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Istradefylline caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [6]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Istradefylline caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [7]
Betrixaban DM2C4RF Moderate Decreased clearance of Istradefylline due to the transporter inhibition by Betrixaban. Venous thromboembolism [BD72] [12]
⏷ Show the Full List of 16 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Crospovidone E00626 Not Available Disintegrant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol E00666 Not Available Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Haematite red E00236 14833 Colorant
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 11 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Istradefylline 20 mg tablet 20 mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Effects of Rifampin on the Pharmacokinetics of a Single Dose of Istradefylline in Healthy Subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201. doi: 10.1002/jcph.1003. Epub 2017 Sep 7.
4 Pharmaceuticals and Medical Devices Agency Japan: Report on Istradefylline
5 Effects of rifampin on the pharmacokinetics of a single dose of istradefylline in healthy subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201.
6 Product Information. Nourianz (istradefylline). Kyowa Kirin, Inc, Bedminster, NJ.
7 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
8 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
9 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
10 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
11 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
12 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.