Details of the Drug

General Information of Drug (ID: DMU3DNC)

• Drug Name: Pentoxifylline
• Synonyms: Agapurin; Azupentat; Dimethyloxohexylxanthine; Durapental; Hemovas; Ikomio; Oxpentifylline; PENTOXYPHYLINE;PNX; Pentoxifilina; Pentoxifyllin; Pentoxifyllinum; Pentoxil; Pentoxiphyllin; Pentoxiphylline; Pentoxiphyllium; Pentoxyfylline; Pentoxyphyllin; Pentoxyphylline; Ralofect; Rentylin; Torental; Trental;Vasofirin; Vazofirin; Agapurin Retard; BL 191; BL191; EHT 0201; EHT0201; IN1161; P 1784; Artal (TN); BL-191; EHT-0201; EHT-201; Flexital (TN); Pentox (TN); Pentoxifilina [INN-Spanish]; Pentoxifyllinum [INN-Latin]; Pentoxil (TN); Pentoxin (TN); Trental (TN); Cis-9-Octadecenoyl coenzyme A; Pentoxifylline [USAN:INN:JAN]; Pentoxifylline (JAN/USP/INN); 1,2,3,6-Tetrahydro-3,7-dimethyl-1-(5-oxohexyl)-2,6-purindion; 1-(5-Oxohexyl)-3,7-dimethylxanthine; 1-(5-Oxohexyl)theobromine; 3,7-Dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-purine-2,6-dione; 3,7-Dimethyl-1-(5-oxo-hexyl)-3,7-dihydro-purine-2,6-dione; 3,7-Dimethyl-1-(5-oxohexyl) xantine; 3,7-Dimethyl-1-(5-oxohexyl)-1H,3H-purin-2,6-dione; 3,7-Dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione; 3,7-Dimethyl-1-(5-oxohexyl)xanthine; 3,7-Dimethyl-1-(5-oxohexyl)xantine; 3,7-dimethyl-1-(5-oxohexyl)purine-2,6-dione

Indication

Disease Entry	ICD 11	Status	REF
Alcoholic hepatitis	DB94.1	Approved	[1]
Intermittent claudication	BD40.00	Approved	[2]
Type-1 diabetes	5A10	Approved	[1]
Peripheral vascular disease	BD4Z	Investigative	[1]

• Therapeutic Class: Vasodilator Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 278.31
  Logarithm of the Partition Coefficient (xlogp); 0.3
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 39 mL/min/kg [4]
  Elimination: 0% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.2 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 71.86143 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.51% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.8 L/kg [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 191 mg/mL [3]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Blood and lymphatic system disorders	Not Available	THBD	OT8VHLKY	[6]
Cell death	Not Available	PRF1	OTFVXD7H	[6]
Cell death	Not Available	GZMB	OTPPVIRS	[6]
Collagen disorder	Not Available	MMP14	OT9C197Z	[6]
Inflammation	Not Available	TNF	OT4IE164	[6]
Inflammation	Not Available	IL1A	OTPSGILV	[6]
Inflammation	Not Available	IL6	OTUOSCCU	[6]
Iron and trace metal metabolism disorders	Not Available	TIMP1	OTOXC51H	[6]

• Chemical Identifiers:
  Formula: C13H18N4O3
  IUPAC Name: 3,7-dimethyl-1-(5-oxohexyl)purine-2,6-dione
  Canonical SMILES: CC(=O)CCCCN1C(=O)C2=C(N=CN2C)N(C1=O)C
  InChI: InChI=1S/C13H18N4O3/c1-9(18)6-4-5-7-17-12(19)10-11(14-8-15(10)2)16(3)13(17)20/h8H,4-7H2,1-3H3
  InChIKey: BYPFEZZEUUWMEJ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4740
  ChEBI ID: CHEBI:7986
  CAS Number: 6493-05-6
  DrugBank ID: DB00806
  TTD ID: D09QEI
  INTEDE ID: DR1255
  ACDINA ID: D00517
• 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
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	Not Available	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Granzyme B (GZMB)	OTPPVIRS	GRAB_HUMAN	Drug Response	[6]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Drug Response	[6]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Drug Response	[6]
Matrix metalloproteinase-14 (MMP14)	OT9C197Z	MMP14_HUMAN	Drug Response	[6]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Drug Response	[6]
Perforin-1 (PRF1)	OTFVXD7H	PERF_HUMAN	Drug Response	[6]
Thrombomodulin (THBD)	OT8VHLKY	TRBM_HUMAN	Drug Response	[6]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Drug Response	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Alcoholic hepatitis
• ICD Disease Classification: DB94.1

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tumor necrosis factor (TNF)	DTT	TNF	8.51E-01	0.05	0.27
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	1.78E-01	-1.19E-01	-1.50E+00
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	4.96E-02	5.36E-01	1.70E+00

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
D&C red no. 30	E00456	3000709	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Sunset yellow FCF	E00255	17730	Colorant
FD&C red no. 3	E00629	Not Available	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pentoxifylline 400 mg tablet	400 mg	Extended Release Oral Tablet	Oral
Pentoxifylline 400 mg tablet	400 mg	Extended Release Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Pentoxifylline FDA Label
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7095).
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [7] Targeted therapies in myelodysplastic syndromes: ASH 2003 review. Semin Hematol. 2004 Apr;41(2 Suppl 4):13-20.
• [8] Cytochrome P450 isozymes involved in lisofylline metabolism to pentoxifylline in human liver microsomes. Drug Metab Dispos. 1997 Dec;25(12):1354-8.