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]

• Drug Type: Small molecular drug
• #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: CHEBI:134726
  CAS Number: 155270-99-8
  DrugBank ID: DB11757
  TTD ID: D0F4ZY
  VARIDT ID: DR00611
  INTEDE ID: DR0892
  ACDINA ID: D01185
• 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]

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]

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

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.