- Accession Number
- DB00235 (APRD00010)
- Small Molecule
A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the ionotropic potency of amrinone. [PubChem]
- External IDs
- WIN 47,203-2
- Product Ingredients
Ingredient UNII CAS InChI Key Milrinone Lactate 9K8XR81MO8 100286-97-3 VWUPWEAFIOQCGF-UHFFFAOYSA-N
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Milrinone Injection Solution 1 mg Intravenous Teva 2003-05-25 2015-07-22 Milrinone Lactate Injection, solution 1 mg/1mL Intravenous Hospira, Inc. 2006-07-17 2006-07-17 Milrinone Lactate in Dextrose Injection 200 ug/1mL Intravenous Baxter Healthcare Corporation 2006-07-27 2006-07-27 Milrinone Lactate Injection Solution 1 mg Intravenous Mylan Pharmaceuticals Not applicable Not applicable Milrinone Lactate Injection Solution 1.0 mg Intravenous Sandoz Canada Incorporated 2003-06-25 Not applicable Milrinone Lactate Injection Solution 1 mg Intravenous Fresenius Kabi 2003-07-03 Not applicable Milrinone Lactate Injection Solution 1 mg Intravenous Sterimax Inc Not applicable Not applicable Milrinone Lactate Injection Solution 1 mg Intravenous Auro Pharma Inc Not applicable Not applicable Primacor Injection, solution 200 ug/1mL Intravenous Sanofi-Synthelabo Inc. 2006-05-10 2018-10-11 Primacor Injection, solution 1 mg/1mL Intravenous Sanofi-Synthelabo Inc. 2006-05-10 2018-10-11
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Apo-milrinone Injectable Solution 1.0 mg Intravenous Apotex Corporation 2005-07-29 2013-08-02 Milrinone Lactate Injection, solution 50 mg/50mL Intravenous West Ward Pharmaceutical 2010-12-03 Not applicable Milrinone Lactate Injection, solution 1 mg/1mL Intravenous Hikma Farmaceutica 2010-12-03 2010-12-03 Milrinone Lactate Injection, solution 1 mg/1mL Intravenous Fresenius Kabi 2002-08-01 Not applicable Milrinone Lactate Injection, solution 200 ug/1mL Intravenous Hikma Farmaceutica 2010-01-21 2010-01-21 Milrinone Lactate Injection 1 mg/1mL Intravenous Bedford Pharmaceuticals 2002-05-27 2011-10-31 Milrinone Lactate Injection, solution 1 mg/1mL Intravenous Hospira Worldwide, Inc. 2002-05-28 2009-04-05 Milrinone Lactate Injection, solution 1 mg/1mL Intravenous Teva Parenteral Medicines, Inc. 2003-06-20 2005-04-30 Milrinone Lactate Injection, solution 1 mg/1mL Intravenous Hospira, Inc. 2015-03-31 Not applicable Milrinone Lactate Injection 1 mg/1mL Intravenous Bedford Pharmaceuticals 2002-05-27 2012-02-29
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Milrinone Lactate in Dextrose Milrinone Lactate (200 ug/1mL) + D-glucose monohydrate (49.4 mg/1mL) Injection Intravenous B. Braun Medical Inc. 2007-10-29 Not applicable
- International/Other Brands
- Corotrop / Corotrope / Milrila / Primacor
- CAS number
- Average: 211.2194
- Chemical Formula
- InChI Key
- IUPAC Name
Indicated for the treatment of congestive heart failure.
- Associated Conditions
Milrinone, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, is used in the treatment of peripheral vascular diseases and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.
- Mechanism of action
Milrinone inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, Milrinone also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity.
Target Actions Organism AcGMP-inhibited 3',5'-cyclic phosphodiesterase Ainhibitor Human
Milrinone is rapidly and almost completely absorbed after oral administration. Bioavailability is 92% (in healthy volunteers).
- Volume of distribution
- 0.38 liters/kg [intravenous injections of 12.5 mcg/kg to 125 mcg/kg to congestive heart failure patients]
- 0.45 liters/kg [intravenous infusions of 0.20 mcg/kg/min to 0.70 mcg/kg/min to congestive heart failure patients]
- Protein binding
70 to 80%
There are five metabolites but the O-glucuronide represents the major pathway of biotransformation.
- Route of elimination
The primary route of excretion of milrinone in man is via the urine.
- Half life
- 0.13 L/kg/hr [congestive heart failure patients, following IV injections of 12.5 mcg/kg to 125 mcg/kg]
- 0.14 L/kg/hr [congestive heart failure patients, following infusions of 0.2 mcg/kg/min to 0.7 mcg/kg/min]
LD50 = 0.3 mg/L in rats
- Affected organisms
- Humans and other mammals
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction Abacavir Milrinone may decrease the excretion rate of Abacavir which could result in a higher serum level. Acarbose Milrinone may decrease the excretion rate of Acarbose which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Milrinone which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Milrinone which could result in a higher serum level. Acetaminophen Milrinone may decrease the excretion rate of Acetaminophen which could result in a higher serum level. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Milrinone which could result in a higher serum level. Aclidinium Milrinone may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Milrinone may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Milrinone which could result in a higher serum level. Adefovir Adefovir may decrease the excretion rate of Milrinone which could result in a higher serum level.
- Food Interactions
- Not Available
- General References
- Not Available
- External Links
- ATC Codes
- C01CE02 — Milrinone
- AHFS Codes
- 24:04.08 — Cardiotonic Agents
- PDB Entries
- FDA label
- Download (491 KB)
- Download (34.8 KB)
- Clinical Trials
- App pharmaceuticals llc
- Baxter healthcare corp anesthesia and critical care
- Baxter healthcare corp anesthesia critical care
- Bedford laboratories div ben venue laboratories inc
- Bioniche pharma usa llc
- Claris lifesciences ltd
- Gland pharma ltd
- Hospira inc
- International medicated systems ltd
- B braun medical inc
- Baxter healthcare corp
- Bedford laboratories
- Hikma farmaceutica (portugal) sa
- Sanofi aventis us llc
- Alchymars SPA
- Apotex Inc.
- APP Pharmaceuticals
- B. Braun Melsungen AG
- Baxter International Inc.
- Bedford Labs
- Ben Venue Laboratories Inc.
- Bioniche Pharma
- Cardinal Health
- Hospira Inc.
- Sanofi-Aventis Inc.
- Teva Pharmaceutical Industries Ltd.
- Dosage forms
Form Route Strength Injection Intravenous 1 mg/1mL Injection Intravenous 20 mg/100mL Injection, solution Intravenous 10 mg/10mL Injection, solution Intravenous 20 mg/20mL Injection, solution Intravenous 50 mg/50mL Injection Intravenous Injection Intravenous 200 ug/1mL Injection, solution Intravenous 0.2 mg/1mL Solution Intravenous 1.0 mg Injection, solution Intravenous 1 mg/1mL Injection, solution Intravenous 200 ug/1mL Solution Intravenous 1 mg
Unit description Cost Unit Primacor 0.2 mg/ml-d5w 100 ml 1.6USD ml Milrinone-d5w 20 mg/100 ml 1.45USD ml Milrinone lact 20 mg/20 ml vial 1.44USD ml Milrinone lact 10 mg/10 ml vial 1.31USD mlDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
- Not Available
- Experimental Properties
Property Value Source melting point (°C) >300 °C PhysProp water solubility Slightly soluble Not Available logP 0.4 Not Available
- Predicted Properties
Property Value Source Water Solubility 0.209 mg/mL ALOGPS logP 1.04 ALOGPS logP 0.33 ChemAxon logS -3 ALOGPS pKa (Strongest Acidic) 7.54 ChemAxon pKa (Strongest Basic) 4.82 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 65.78 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 61.14 m3·mol-1 ChemAxon Polarizability 21.46 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon
- Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9807 Caco-2 permeable + 0.6889 P-glycoprotein substrate Non-substrate 0.8041 P-glycoprotein inhibitor I Non-inhibitor 0.7835 P-glycoprotein inhibitor II Non-inhibitor 0.9799 Renal organic cation transporter Non-inhibitor 0.8614 CYP450 2C9 substrate Non-substrate 0.7016 CYP450 2D6 substrate Non-substrate 0.8411 CYP450 3A4 substrate Non-substrate 0.5641 CYP450 1A2 substrate Inhibitor 0.5399 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9816 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8827 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7866 Ames test Non AMES toxic 0.7822 Carcinogenicity Non-carcinogens 0.9351 Biodegradation Not ready biodegradable 0.993 Rat acute toxicity 2.5820 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.991 hERG inhibition (predictor II) Non-inhibitor 0.8941
- Mass Spec (NIST)
- Not Available
- This compound belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Pyridines and derivatives
- Sub Class
- Bipyridines and oligopyridines
- Direct Parent
- Bipyridines and oligopyridines
- Alternative Parents
- 3-pyridinecarbonitriles / Methylpyridines / Hydroxypyridines / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
- Bipyridine / 3-pyridinecarbonitrile / Methylpyridine / Hydroxypyridine / Heteroaromatic compound / Azacycle / Nitrile / Carbonitrile / Organic nitrogen compound / Organic oxygen compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- nitrile, pyridone, bipyridines (CHEBI:50693)
- Pharmacological action
- General Function
- Metal ion binding
- Specific Function
- Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
- Gene Name
- Uniprot ID
- Uniprot Name
- cGMP-inhibited 3',5'-cyclic phosphodiesterase A
- Molecular Weight
- 124978.06 Da
- Cone J, Wang S, Tandon N, Fong M, Sun B, Sakurai K, Yoshitake M, Kambayashi J, Liu Y: Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells. J Cardiovasc Pharmacol. 1999 Oct;34(4):497-504. [PubMed:10511123]
- Kuthe A, Magert H, Uckert S, Forssmann WG, Stief CG, Jonas U: Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis. Eur Urol. 2000 Jul;38(1):108-14. [PubMed:10859452]
- Lefievre L, de Lamirande E, Gagnon C: Presence of cyclic nucleotide phosphodiesterases PDE1A, existing as a stable complex with calmodulin, and PDE3A in human spermatozoa. Biol Reprod. 2002 Aug;67(2):423-30. [PubMed:12135876]
- Zhang W, Ke H, Colman RW: Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis. Mol Pharmacol. 2002 Sep;62(3):514-20. [PubMed:12181427]
- Shakur Y, Fong M, Hensley J, Cone J, Movsesian MA, Kambayashi J, Yoshitake M, Liu Y: Comparison of the effects of cilostazol and milrinone on cAMP-PDE activity, intracellular cAMP and calcium in the heart. Cardiovasc Drugs Ther. 2002 Sep;16(5):417-27. [PubMed:12652111]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:39