Details of the Drug

General Information of Drug (ID: DMHR8KW)

• Drug Name: Alvimopan
• Synonyms: Alvimopan anhydrous; LY 246736; LY246736; Adl 8-2698; Entereg (TN); Trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine; Glycine, N-[2-[[4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-phenylpropyl; 2-[[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl]amino]acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Gastrointestinal disease	DE2Z	Approved	[1]

• Therapeutic Class: Analgesics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 424.5
  Logarithm of the Partition Coefficient (xlogp); 1.7
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Clearance: The clearance of drug is 402 +/- 89 mL/min []
  Elimination: 2% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 10 - 17 hours [3]
  Metabolism: The drug is metabolized via the intestinal flora to an active metabolite []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.8076 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.2% [3]
  Vd: The volume of distribution (Vd) of drug is 30 +/- 10 L []
  Water Solubility: The ability of drug to dissolve in water is measured as 0.1 mg/mL [2]
• Chemical Identifiers:
  Formula: C25H32N2O4
  IUPAC Name: 2-[[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl]amino]acetic acid
  Canonical SMILES: C[C@H]1CN(CC[C@@]1(C)C2=CC(=CC=C2)O)C[C@H](CC3=CC=CC=C3)C(=O)NCC(=O)O
  InChI: InChI=1S/C25H32N2O4/c1-18-16-27(12-11-25(18,2)21-9-6-10-22(28)14-21)17-20(24(31)26-15-23(29)30)13-19-7-4-3-5-8-19/h3-10,14,18,20,28H,11-13,15-17H2,1-2H3,(H,26,31)(H,29,30)/t18-,20-,25+/m0/s1
  InChIKey: UPNUIXSCZBYVBB-JVFUWBCBSA-N
• Cross-matching ID:
  PubChem CID: 5488548
  ChEBI ID: CHEBI:135686
  CAS Number: 156053-89-3
  DrugBank ID: DB06274
  TTD ID: D0D7KC
  ACDINA ID: D00026

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Antagonist	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Protein Interaction/Cellular Processes	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Gastrointestinal disease
• ICD Disease Classification: DE2Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor mu (MOP)	DTT	OPRM1	5.94E-01	-0.02	-0.17

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alvimopan (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Enzalutamide	DMGL19D	Moderate	Accelerated clearance of Alvimopan due to the transporter induction by Enzalutamide.	Prostate cancer [2C82]	[7]
Fostamatinib	DM6AUHV	Moderate	Decreased clearance of Alvimopan due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[8]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Alvimopan 12 mg capsule	12 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] 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: 7471).
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] 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
• [5] Alvimopan for postoperative ileus. Am J Health Syst Pharm. 2009 Jul 15;66(14):1267-77.
• [6] The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone. Naunyn Schmiedebergs Arch Pharmacol. 2007 May;375(3):205-20. doi: 10.1007/s00210-007-0146-x. Epub 2007 Mar 6.
• [7] Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
• [8] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.