Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameHydromorphone
Accession NumberDB00327  (APRD01021)
Typesmall molecule
Groupsapproved, illicit
Description

An opioid analgesic derived from morphine and used mainly as an analgesic. It has a shorter duration of action and is more potent than morphine. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
6-Deoxy-7,8-dihydro-6-oxomorphineNot AvailableNot Available
7,8-DihydromorphinoneNot AvailableNot Available
DihydromorfinonCzechNot Available
DihydromorphinoneNot AvailableNot Available
DimorphoneNot AvailableNot Available
HidromorfonaSpanishINN
HydromorfonaSpanishNot Available
HydromorphonumLatinINN
IdromorfoneItalianNot Available
Salts
Name/CAS Structure Properties
Hydromorphone Hydrochloride
71-68-1
Thumb
  • InChI Key: XHILEZUETWRSHC-NRGUFEMZSA-N
  • Monoisotopic Mass: 321.113171218
  • Average Mass: 321.799
DBSALT000444
Brand names
NameCompany
DilaudidNot Available
PalladoneNot Available
Brand mixturesNot Available
Categories
CAS number466-99-9
WeightAverage: 285.3377
Monoisotopic: 285.136493479
Chemical FormulaC17H19NO3
InChI KeyInChIKey=WVLOADHCBXTIJK-YNHQPCIGSA-N
InChI
InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,16,19H,3,5-8H2,1H3/t10-,11+,16-,17-/m0/s1
IUPAC Name
(1S,5R,13R,17R)-10-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one
SMILES
[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])CCC2=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassMorphinans
SubclassNot Available
Direct parentMorphinans
Alternative parentsBenzylisoquinolines; Phenanthrenes and Derivatives; Isoquinolones and Derivatives; Tetralins; Benzofurans; Phenols and Derivatives; Cyclohexanones; Alkyl Aryl Ethers; Piperidines; Tertiary Amines; Polyamines; Enols
Substituentsphenanthrene; isoquinolone; tetralin; benzofuran; phenol derivative; alkyl aryl ether; cyclohexanone; piperidine; benzene; ketone; tertiary amine; enol; ether; polyamine; carbonyl group; organonitrogen compound; amine
Classification descriptionThis compound belongs to the morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
Pharmacology
IndicationFor the relief of moderate to severe pain such as that due to surgery, cancer, trauma/injury, or burns.
PharmacodynamicsHydromorphone is a hydrogenated ketone derivative of morphine that acts as a narcotic analgesic. It has a shorter duration of action than morphine. Hydromorphone is approximately 8 times more potent on a milligram basis than morphine. In addition, hydromorphone is better absorbed orally than is morphine. In clinical settings, Hydromorphone exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Hydromorphone appears to increase the patient's tolerance for pain and to decrease discomfort, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Opioids also produce respiratory depression by direct action on brain stem respiratory centers.
Mechanism of actionHydromorphone is a narcotic analgesic; its principal therapeutic effect is relief of pain. Hydromorphone interacts predominantly with the opioid mu-receptors. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. In clinical settings, Hydromorphone exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Hydromorphone also binds with kappa-receptors which are thought to mediate spinal analgesia, miosis and sedation.
AbsorptionBetter absorbed orally than morphine
Volume of distributionNot Available
Protein binding20%
Metabolism

Primarily hepatic. After absorption hydromorphone is metabolized by the liver to the glucuronide conjugate which is then excreted in the urine. Hydromorphone is metabolized to the major metabolites hydromorphone-3-glucuronide, hydromorphone-3-glucoside and dihydroisomorphine-6-glucuronide.

SubstrateEnzymesProduct
Hydromorphone
DihydromorphineDetails
Hydromorphone
DihydroisomorphineDetails
Hydromorphone
NorhydromorphoneDetails
Hydromorphone
Hydromorphone 3-beta-O-glucuronideDetails
Hydromorphone
    Dihydroisomorphine-6-glucuronideDetails
    Hydromorphone
      Hydromorphone-3-glucosideDetails
      Hydromorphone
        Hydromorphone-3-glucuronideDetails
        Hydromorphone
          Hydromorphone-3-sulphateDetails
          Dihydromorphine
          Dihydromorphine-3-glucuronideDetails
          Route of eliminationOnly a small amount of the hydromorphone dose is excreted unchanged in the urine. Most of the dose is excreted as hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.
          Half life2.6 hours (oral); 18.6 hours for sustained release Palladone
          Clearance
          • 1.96 L/min
          ToxicityHydromorphone is a schedule II narcotic which can lead to physical dependence or addiction. High doses lead to respiratory depression, nausea, and vomiting. Overdoses lead to extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.
          Affected organisms
          • Humans and other mammals
          Pathways
          PathwayCategorySMPDB ID
          Hydromorphone Action PathwayDrug actionSMP00410
          SNP Mediated EffectsNot Available
          SNP Mediated Adverse Drug ReactionsNot Available
          ADMET
          Predicted ADMET features
          Property Value Probability
          Human Intestinal Absorption + 1.0
          Blood Brain Barrier + 0.9931
          Caco-2 permeable + 0.8647
          P-glycoprotein substrate Substrate 0.8174
          P-glycoprotein inhibitor I Non-inhibitor 0.8497
          P-glycoprotein inhibitor II Non-inhibitor 0.9641
          Renal organic cation transporter Inhibitor 0.6374
          CYP450 2C9 substrate Non-substrate 0.7925
          CYP450 2D6 substrate Substrate 0.8618
          CYP450 3A4 substrate Substrate 0.7571
          CYP450 1A2 substrate Non-inhibitor 0.6918
          CYP450 2C9 substrate Non-inhibitor 0.9539
          CYP450 2D6 substrate Non-inhibitor 0.5197
          CYP450 2C19 substrate Non-inhibitor 0.8088
          CYP450 3A4 substrate Non-inhibitor 0.8177
          CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9413
          Ames test Non AMES toxic 0.7214
          Carcinogenicity Non-carcinogens 0.9554
          Biodegradation Not ready biodegradable 0.9815
          Rat acute toxicity 2.9191 LD50, mol/kg Not applicable
          hERG inhibition (predictor I) Weak inhibitor 0.8906
          hERG inhibition (predictor II) Non-inhibitor 0.8992
          Pharmacoeconomics
          Manufacturers
          • Purdue pharma lp
          • Purdue pharmaceutical products lp
          • Akorn inc
          • Barr laboratories inc
          • Hospira inc
          • Watson laboratories inc
          • Roxane laboratories inc
          • Mallinckrodt inc
          • Actavis totowa llc
          • Kv pharmaceutical co
          • Lannett holdings inc
          • Tyco healthcare mallinckrodt
          Packagers
          Dosage forms
          FormRouteStrength
          Capsule, extended releaseOral
          LiquidIntramuscular
          LiquidIntravenous
          LiquidOral
          Powder, for solutionIntravenous
          SolutionIntravenous
          SuppositoryRectal
          SyrupOral
          TabletOral
          Prices
          Unit descriptionCostUnit
          Hydromorphone hcl powder166.25USDg
          Dilaudid-hp 250 mg vial114.8USDvial
          Dilaudid Sterile Powder 250 mg/vial78.99USDvial
          HYDROmorphone HCl 6 3 mg Suppository Box54.92USDbox
          Hydromorphone Hp 50 50 mg/ml13.78USDml
          Dilaudid-Xp 50 mg/ml11.82USDml
          Hydromorphone 3 mg suppository11.11USDsuppository
          Dilaudid-Hp-Plus 20 mg/ml5.08USDml
          Hydromorphone Hp 20 20 mg/ml4.72USDml
          Hydromorph Contin 30 mg Controlled-Release Capsule4.21USDcapsule
          Hydromorph Contin 24 mg Controlled-Release Capsule3.52USDcapsule
          Dilaudid-Hp 10 mg/ml3.14USDml
          Hydromorphone Hp 10 mg/ml2.92USDml
          Hydromorph Contin 18 mg Controlled-Release Capsule2.75USDcapsule
          Hydromorphone 10 mg/ml ampul2.58USDml
          Pms-Hydromorphone 3 mg Suppository2.42USDsuppository
          Dilaudid 4 mg/ml ampul2.2USDml
          Dilaudid 8 mg tablet2.19USDtablet
          HYDROmorphone HCl 4 mg/ml Solution 1ml Cartridge2.07USDcartridge
          Hydromorph Contin 12 mg Controlled-Release Capsule1.91USDcapsule
          Dilaudid 2 mg/ml ampul1.81USDml
          Dilaudid 1 mg/ml ampul1.64USDml
          Hydromorphone hcl 8 mg tablet1.4USDtablet
          Dilaudid 4 mg tablet1.36USDtablet
          Hydromorphone 8 mg tablet1.32USDtablet
          Dilaudid 2 mg/ml1.28USDml
          Hydromorphone 2 mg/ml1.19USDml
          Hydromorph Contin 6 mg Controlled-Release Capsule1.1USDcapsule
          Hydromorphone-ns 0.4 mg/ml1.08USDml
          Hydromorphone-ns 0.3 mg/ ml1.05USDml
          Hydromorphone 2 mg/ml vial1.02USDml
          Hydromorphone-ns 25 mg/25 ml1.01USDml
          Dilaudid 2 mg tablet1.0USDtablet
          Hydromorphone-ns 2.5 mg/25 ml0.96USDml
          HYDROmorphone HCl 4 mg tablet0.8USDtablet
          HYDROmorphone HCl 2 mg tablet0.77USDtablet
          Hydromorph Contin 3 mg Controlled-Release Capsule0.73USDcapsule
          Hydromorphone 4 mg tablet0.72USDtablet
          Dilaudid 8 mg Tablet0.55USDtablet
          Hydromorphone-ns 0.2 mg/ml0.49USDml
          Hydromorphone 2 mg tablet0.37USDtablet
          Pms-Hydromorphone 8 mg Tablet0.37USDtablet
          Dilaudid 4 mg Tablet0.35USDtablet
          Dilaudid-5 1 mg/ml liquid0.33USDml
          Hydromorphone-ns 5.5 mg/55 ml0.33USDml
          Dilaudid 2 mg Tablet0.23USDtablet
          Pms-Hydromorphone 4 mg Tablet0.23USDtablet
          Dilaudid 1 mg Tablet0.16USDtablet
          Pms-Hydromorphone 2 mg Tablet0.15USDtablet
          Pms-Hydromorphone 1 mg Tablet0.1USDtablet
          Dilaudid 1 mg/ml Liquid0.09USDml
          Pms-Hydromorphone 1 mg/ml Liquid0.07USDml
          DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
          Patents
          CountryPatent NumberApprovedExpires (estimated)
          United States65899602000-11-092020-11-09
          United States59685511994-12-242011-12-24
          Properties
          Statesolid
          Experimental Properties
          PropertyValueSource
          melting point266.5 °CPhysProp
          logP0.9Not Available
          Predicted Properties
          PropertyValueSource
          water solubility4.39e+00 g/lALOGPS
          logP1.69ALOGPS
          logP1.62ChemAxon
          logS-1.8ALOGPS
          pKa (strongest acidic)10.11ChemAxon
          pKa (strongest basic)8.59ChemAxon
          physiological charge1ChemAxon
          hydrogen acceptor count4ChemAxon
          hydrogen donor count1ChemAxon
          polar surface area49.77ChemAxon
          rotatable bond count0ChemAxon
          refractivity78.26ChemAxon
          polarizability30.02ChemAxon
          number of rings5ChemAxon
          bioavailability1ChemAxon
          rule of fiveYesChemAxon
          Ghose filterYesChemAxon
          Veber's ruleNoChemAxon
          MDDR-like ruleNoChemAxon
          Spectra
          SpectraNot Available
          References
          Synthesis Reference

          Anne M. Hailes, Christopher E. French, Neil C. Bruce, “Morphinone reductase for the preparation of hydromorphone and hydrocodone.” U.S. Patent US5571685, issued November, 1990.

          US5571685
          General Reference
          1. Coda BA, Rudy AC, Archer SM, Wermeling DP: Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg. 2003 Jul;97(1):117-23, table of contents. Pubmed
          2. Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL: Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects. J Clin Pharmacol. 1981 Apr;21(4):152-6. Pubmed
          External Links
          ResourceLink
          KEGG CompoundC07042
          PubChem Compound5284570
          PubChem Substance46508700
          ChemSpider4447624
          ChEBI5790
          ChEMBLCHEMBL398707
          Therapeutic Targets DatabaseDAP000472
          PharmGKBPA449918
          Drug Product Database2249936
          RxListhttp://www.rxlist.com/cgi/generic/hydromorphone.htm
          Drugs.comhttp://www.drugs.com/cdi/hydromorphone.html
          PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dil1137.shtml
          WikipediaHydromorphone
          ATC CodesN02AA03
          AHFS Codes
          • 28:08.08
          PDB EntriesNot Available
          FDA labelshow(78.9 KB)
          MSDSshow(48.3 KB)
          Interactions
          Drug Interactions
          Drug
          AlvimopanIncreases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
          EltrombopagIncreases levels of Hydromorphone via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
          TriprolidineThe CNS depressants, Triprolidine and Hydromorphone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
          Food Interactions
          • Take without regard to meals. Avoid alcohol.

          1. Mu-type opioid receptor

          Kind: protein

          Organism: Human

          Pharmacological action: yes

          Actions: agonist

          Components

          Name UniProt ID Details
          Mu-type opioid receptor P35372 Details

          References:

          1. Quigley C: Hydromorphone for acute and chronic pain. Cochrane Database Syst Rev. 2002;(1):CD003447. Pubmed
          2. Inturrisi CE: Clinical pharmacology of opioids for pain. Clin J Pain. 2002 Jul-Aug;18(4 Suppl):S3-13. Pubmed
          3. Sarhill N, Walsh D, Nelson KA: Hydromorphone: pharmacology and clinical applications in cancer patients. Support Care Cancer. 2001 Mar;9(2):84-96. Pubmed
          4. Kumar P, Sunkaraneni S, Sirohi S, Dighe SV, Walker EA, Yoburn BC: Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation. Eur J Pharmacol. 2008 Nov 12;597(1-3):39-45. Epub 2008 Aug 30. Pubmed

          2. Delta-type opioid receptor

          Kind: protein

          Organism: Human

          Pharmacological action: yes

          Actions: partial agonist

          Components

          Name UniProt ID Details
          Delta-type opioid receptor P41143 Details

          References:

          1. Fang X, Larson DL, Portoghese PS: 7-spirobenzocyclohexyl derivatives of naltrexone, oxymorphone, and hydromorphone as selective opioid receptor ligands. J Med Chem. 1997 Sep 12;40(19):3064-70. Pubmed
          2. Hennies HH, Friderichs E, Schneider J: Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittelforschung. 1988 Jul;38(7):877-80. Pubmed
          3. Jiang Q, Sebastian A, Archer S, Bidlack JM: 5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone and its corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta-methyl-14 beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone: mu-selective irreversible opioid antagonists. J Pharmacol Exp Ther. 1994 Mar;268(3):1107-13. Pubmed
          4. Guay DR: Use of oral oxymorphone in the elderly. Consult Pharm. 2007 May;22(5):417-30. Pubmed
          5. Hartvig P, Neil A, Terenius L, Antoni G, Rimland A, Ulin J, Langstrom B: Brain and plasma kinetics of the opioid 11C-hydromorphone in two macaque species. Pharmacol Toxicol. 1989 Sep;65(3):214-6. Pubmed
          6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

          3. Kappa-type opioid receptor

          Kind: protein

          Organism: Human

          Pharmacological action: yes

          Actions: agonist

          Components

          Name UniProt ID Details
          Kappa-type opioid receptor P41145 Details

          References:

          1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
          2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
          3. Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J: Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3. Pubmed

          1. Cytochrome P450 3A4

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 3A4 P08684 Details

          References:

          1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
          2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          2. Cytochrome P450 2C9

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 2C9 P11712 Details

          References:

          1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
          2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          3. Cytochrome P450 2D6

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 2D6 P10635 Details

          References:

          1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
          2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          4. Prostaglandin G/H synthase 1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Prostaglandin G/H synthase 1 P23219 Details

          References:

          1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

          5. UDP-glucuronosyltransferase 1-9

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          UDP-glucuronosyltransferase 1-9 O60656 Details

          References:

          1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

          Comments
          Drug created on June 13, 2005 07:24 / Updated on January 20, 2014 21:22