milrinone 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
cardiac stimulants, amrinone derivatives 1809 78415-72-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • primacor
  • milrinone
  • corotrop
  • corotrope
  • milrinone lactate
A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.
  • Molecular weight: 211.22
  • Formula: C12H9N3O
  • CLOGP: -0.03
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 1
  • TPSA: 65.78
  • ALOGS: -3
  • ROTB: 1
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
50 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 4 Bocci G, Oprea TI, Benet LZ
S (Water solubility) 0.21 mg/mL Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 85 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.35 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 86 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.25 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 6.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.04 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.80 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.177 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 13.490 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 9.750 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 3.311 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 65.110 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 73.860 % High 1
herg hERG pIC50 4.062 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.125 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.184 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 54.020 % High 1
kinase-safety-class ACVR2A,ACVR2B,ALK,AURKA,AURKB,AURKC,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK19,CDK2,CDK5,CDK7,CDK9,CHEK1,CLK4,DDR1,DYRK1A,DYRK1B,EGFR,EIF2AK3,ERBB2,FLT3,GRK1,GRK2,GRK3,GSK3B,IKBKB,IRAK1,ITK,JAK1,MAP3K10,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK7,MAPK9,MARK4,MET,PDK1,PDK2,PDK4,PIK3CB,PIK3CD,PRKCD,PRKDC,SGK1,SIK2,SIK3,STK33,SYK,TEK,TNIK,TTK,ULK1,ULK2 60
kinase-selectivity-class ACVR2A,ACVR2B,AXL,BRAF,CAMK2B,CAMK2D,CDK9,DYRK1A,DYRK1B,ERBB2,GRK2,MAPK7,MARK4,MINK1,PRKDC,SIK2,STK33,TNIK 18
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 2.312 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 5.768 High 1
mh-clint Mouse hepatocyte intrinsic clearance 13.459 High 1
mppb Mouse plasma protein binding (% unbound) 65.630 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 9.099 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 71.290 % High 1
rat-kpuu-brain Rat brain Kpuu 0.048 % High 1
rh-clint Rat hepatocyte intrinsic clearance 3.373 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 92.810 % High 1
rppb Rat plasma protein binding (% unbound) 38.630 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 504.661 uM High 1

Approvals:

DateAgencyCompanyOrphan
Dec. 31, 1987 FDA SANOFI AVENTIS US

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug ineffective 184.34 42.78 201 2188 1384097 89241961
Drug ineffective for unapproved indication 106.37 42.78 46 2343 66598 90559460
Cardiogenic shock 89.89 42.78 31 2358 24437 90601621
Ventricular tachycardia 89.59 42.78 31 2358 24677 90601381
Cardiac arrest 83.66 42.78 45 2344 104890 90521168
Hypotension 80.02 42.78 67 2322 325330 90300728
Respiratory failure 73.24 42.78 43 2346 118375 90507683
Pulmonary hypertension 69.91 42.78 30 2359 42493 90583565
Cardiac failure chronic 68.53 42.78 18 2371 5628 90620430
Right ventricular dysfunction 61.91 42.78 14 2375 2350 90623708
Right ventricular failure 61.58 42.78 22 2367 19183 90606875
Bronchopulmonary dysplasia 60.60 42.78 11 2378 613 90625445
Pulmonary hypertensive crisis 56.82 42.78 10 2379 467 90625591
Multiple organ dysfunction syndrome 56.35 42.78 30 2359 68306 90557752
Off label use 55 42.78 101 2288 1102151 89523907
Neurodevelopmental disorder 48.74 42.78 8 2381 245 90625813
Cardiomyopathy 45.96 42.78 18 2371 20188 90605870

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug ineffective 309.28 33.74 257 2032 629940 41989106
Cardiogenic shock 60.24 33.74 32 2257 35608 42583438
Cardiac index decreased 40.40 33.74 6 2283 43 42619003
Pulmonary haemorrhage 40.18 33.74 17 2272 11380 42607666
Cardiac arrest 37.20 33.74 37 2252 109283 42509763
Shock 35.19 33.74 21 2268 29100 42589946
Posthaemorrhagic hydrocephalus 34.74 33.74 6 2283 120 42618926

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug ineffective 434.45 32.59 394 3805 1520146 109064954
Cardiogenic shock 144.90 32.59 61 4138 57277 110527823
Ventricular tachycardia 119.01 32.59 51 4148 49958 110535142
Cardiac arrest 106.01 32.59 75 4124 196678 110388422
Drug ineffective for unapproved indication 102.75 32.59 58 4141 102780 110482320
Pulmonary hypertension 89.19 32.59 43 4156 55177 110529923
Hypotension 88.78 32.59 104 4095 523745 110061355
Right ventricular failure 83.98 32.59 33 4166 25921 110559179
Cardiac failure chronic 80.02 32.59 27 4172 13784 110571316
Multiple organ dysfunction syndrome 59.74 32.59 48 4151 151662 110433438
Right ventricular dysfunction 56.83 32.59 15 4184 3308 110581792
Cardiomyopathy 56.82 32.59 27 4172 33498 110551602
Respiratory failure 56.37 32.59 54 4145 215278 110369822
Off label use 55.25 32.59 152 4047 1500033 109085067
Heparin-induced thrombocytopenia 53.29 32.59 19 4180 11405 110573695
Shock 52.85 32.59 30 4169 53558 110531542
Cardiac failure 50.90 32.59 48 4151 187578 110397522
Cardiac index decreased 41.69 32.59 7 4192 169 110584931
Condition aggravated 40.26 32.59 87 4112 734749 109850351
Cardiac failure acute 36.59 32.59 18 4181 24060 110561040
Torsade de pointes 34.66 32.59 17 4182 22583 110562517
Acute kidney injury 34.50 32.59 75 4124 635355 109949745
Platelet aggregation inhibition 33.75 32.59 6 4193 204 110584896

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C01CE02 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
CARDIAC STIMULANTS EXCL. CARDIAC GLYCOSIDES
Phosphodiesterase inhibitors
FDA MoA N0000175086 Phosphodiesterase 3 Inhibitors
FDA EPC N0000175598 Phosphodiesterase 3 Inhibitor
MeSH PA D002316 Cardiotonic Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006401 Hematologic Agents
MeSH PA D010726 Phosphodiesterase Inhibitors
MeSH PA D010975 Platelet Aggregation Inhibitors
MeSH PA D014665 Vasodilator Agents
MeSH PA D020011 Protective Agents
MeSH PA D058987 Phosphodiesterase 3 Inhibitors
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:38147 cardiotonic drug
CHEBI has role CHEBI:50427 platelet aggregation inhibitor
CHEBI has role CHEBI:50568 EC 3.1.4.17 (3,5-cyclic-nucleotide phosphodiesterase) inhibitor
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35674 antihypertensive agent
CHEBI has role CHEBI:53784 antispasmodic drug

Related Drugs by ATC class:

C01CE Phosphodiesterase inhibitors 3 drugs
amrinonebucladesineenoximone

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Decompensated cardiac failure indication 195111005
Myocardial infarction contraindication 22298006 DOID:5844
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Pulmonic valve stenosis contraindication 56786000 DOID:6420
Kidney disease contraindication 90708001 DOID:557
Idiopathic hypertrophic subaortic stenosis contraindication 360465008




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.97 acidic
pKa2 6.24 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Enzyme INHIBITOR IC50 6.36 CHEMBL CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase Enzyme IC50 6.13 CHEMBL
cGMP-inhibited 3',5'-cyclic phosphodiesterase B Enzyme IC50 6.55 CHEMBL
Phosphodiesterase 3 Enzyme Ki 6.82 CHEMBL
Phosphodiesterase 4 Enzyme IC50 5.22 CHEMBL
Cyclic nucleotide phosphodiesterase PDE3A Enzyme IC50 6.07 CHEMBL
Cyclic AMP-specific phosphodiesterase SSPDE4A1A Enzyme IC50 4.89 CHEMBL
Uncharacterized protein Enzyme IC50 6 CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase Enzyme IC50 5.30 CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme Ki 5.33 CHEMBL

External reference:

IDSource
4023601 VUID
N0000021606 NUI
D00417 KEGG_DRUG
100286-97-3 SECONDARY_CAS_RN
4020722 VANDF
4023601 VANDF
C0128513 UMLSCUI
CHEBI:50693 CHEBI
MIL PDB_CHEM_ID
CHEMBL189 ChEMBL_ID
DB00235 DRUGBANK_ID
CHEMBL1200977 ChEMBL_ID
D020105 MESH_DESCRIPTOR_UI
4197 PUBCHEM_CID
5225 IUPHAR_LIGAND_ID
5383 INN_ID
JU9YAX04C7 UNII
155120 RXNORM
43671 MMSL
5116 MMSL
6676 MMSL
d00302 MMSL
004083 NDDF
004084 NDDF
108480007 SNOMEDCT_US
108481006 SNOMEDCT_US
373441005 SNOMEDCT_US
JU9YAX04C7 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9326 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 23 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9373 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9374 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9708 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 24 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9709 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 24 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9710 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 24 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0143-9718 INJECTION, SOLUTION 200 ug INTRAVENOUS ANDA 21 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0143-9719 INJECTION, SOLUTION 200 ug INTRAVENOUS ANDA 21 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0338-6010 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 23 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0338-6011 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 23 sections
MILRINONE LACTATE HUMAN PRESCRIPTION DRUG LABEL 1 0409-0212 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 20 sections
Milrinone Lactate in Dextrose Human Prescription Drug Label 1 0409-1983 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate in Dextrose Human Prescription Drug Label 1 0409-2045 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 25021-313 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 23 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 42677-313 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 12 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 42677-314 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 12 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 42677-338 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 12 sections
Milrinone Lactate Human Prescription Drug Label 1 55150-287 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 21 sections
Milrinone Lactate Human Prescription Drug Label 1 55150-288 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 21 sections
Milrinone Lactate Human Prescription Drug Label 1 63323-617 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 11 sections
Milrinone Lactate Human Prescription Drug Label 1 65145-120 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections
Milrinone Lactate Human Prescription Drug Label 1 65145-121 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections
Milrinone Lactate Human Prescription Drug Label 1 65145-122 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections
Milrinone Lactate in 5% Dextrose Human Prescription Drug Label 1 65145-176 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 21 sections
Milrinone Lactate in 5% Dextrose Human Prescription Drug Label 1 65145-177 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 21 sections
Milrinone Lactate Human Prescription Drug Label 1 68083-318 INJECTION 1 mg INTRAVENOUS ANDA 22 sections
Milrinone Lactate in Dextrose Human Prescription Drug Label 1 68083-410 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate in Dextrose Human Prescription Drug Label 1 68083-411 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate Human Prescription Drug Label 1 70069-807 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections
Milrinone Lactate Human Prescription Drug Label 1 70069-808 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections