Details of the Drug

General Information of Drug (ID: DM8TUPF)

• Drug Name: Milrinone
• Synonyms: Corotrop; Corotrope; Milrila; Milrinona; Milrinonum; Primacor; Milrinona [Spanish]; Milrinonum [Latin]; M 4659; M1663; YM 018; MILRINONE LACTATE IN DEXTROSE 5% IN PLASTIC CONTAINER; Milrila (TN); PRIMACOR IN DEXTROSE 5% IN PLASTIC CONTAINER; Primacor (TN); WIN 47203-2; Win-47203; Milrinone [USAN:BAN:INN]; Win-47203-2; Milrinone (JAN/USAN/INN); 1,6-Dihydro-2-methyl-6-oxo(3,4'-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-(3,4′-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-(3,4'-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile; 111GE027; 2-methyl-6-oxo-1,6-dihydro-3,4'-bipyridine-5-carbonitrile; 3-Cyano-6-methyl-5-(4-pyridyl)-2-pyridone; 6-Methyl-5-(4-pyridyl)-2-pyridone-3-carbonitrile; 6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile

Indication

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[1]
Cardiomyopathy	BC43	Investigative	[2]

• Therapeutic Class: Cardiotonic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 211.22
  Logarithm of the Partition Coefficient (xlogp); 0
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Bioavailability: 86% of drug becomes completely available to its intended biological destination(s) [4]
  Clearance: The clearance of drug is 0.13 L/h/kg [5]
  Elimination: Milrinone is primarily excreted in the urine, with 60% of a dose recovered after two hours and 90% within eight hours [6]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.3 hours (injections between 12.5 - 125 g/kg), and 2.4 hours (infusions between 0.2 - 0.7 g/kg/minutes) [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 5.35 micromolar/kg/day [7]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.035% [8]
  Vd: The volume of distribution (Vd) of drug is 0.38 L/kg [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [3]
• Chemical Identifiers:
  Formula: C12H9N3O
  IUPAC Name: 6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile
  Canonical SMILES: CC1=C(C=C(C(=O)N1)C#N)C2=CC=NC=C2
  InChI: InChI=1S/C12H9N3O/c1-8-11(9-2-4-14-5-3-9)6-10(7-13)12(16)15-8/h2-6H,1H3,(H,15,16)
  InChIKey: PZRHRDRVRGEVNW-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4197
  ChEBI ID: CHEBI:50693
  CAS Number: 78415-72-2
  DrugBank ID: DB00235
  TTD ID: D0Y9ZE
• 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
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Gene/Protein Processing	[10]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Gene/Protein Processing	[11]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Linezolid	DMGFPU2	Moderate	Additive hypotensive effects by the combination of Milrinone and Linezolid.	Bacterial infection [1A00-1C4Z]	[12]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Milrinone and Selegiline.	Depression [6A70-6A7Z]	[12]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Milrinone and Isocarboxazid.	Depression [6A70-6A7Z]	[12]
Tranylcypromine	DMGB5RE	Moderate	Additive hypotensive effects by the combination of Milrinone and Tranylcypromine.	Depression [6A70-6A7Z]	[13]
Phenelzine	DMHIDUE	Moderate	Additive hypotensive effects by the combination of Milrinone and Phenelzine.	Depression [6A70-6A7Z]	[12]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Milrinone and Procarbazine.	Hodgkin lymphoma [2B30]	[12]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Milrinone and Ozanimod.	Multiple sclerosis [8A40]	[12]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Milrinone and Safinamide.	Parkinsonism [8A00]	[12]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Milrinone and Rasagiline.	Parkinsonism [8A00]	[12]
Disopyramide	DM5SYZP	Moderate	Additive hypotensive effects by the combination of Milrinone and Disopyramide.	Ventricular tachyarrhythmia [BC71]	[14]

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: 5225).
• [2] Milrinone FDA Label
• [3] BDDCS applied to over 900 drugs
• [4] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [5] FDA Approved Drug Products: PRIMACOR (milrinone) injection
• [6] Shipley JB, Tolman D, Hastillo A, Hess ML: Milrinone: basic and clinical pharmacology and acute and chronic management. Am J Med Sci. 1996 Jun;311(6):286-91. doi: 10.1097/00000441-199606000-00011.
• [7] 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
• [8] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting. Anesth Analg. 2002 Jan;94(1):22-30, table of contents. doi: 10.1097/00000539-200201000-00005.
• [11] Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells. Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):410-8. doi: 10.1165/rcmb.2002-0247OC. Epub 2003 Apr 24.
• [12] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
• [13] Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
• [14] Product Information. Inocor (inamrinone). Sanofi Winthrop Pharmaceuticals, New York, NY.