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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
(-)-(5R)-4,5-Epoxy-3-hydroxy-9alpha-methylmorphinan-6-oneNot AvailableNot Available
4,5-Epoxy-3-hydroxy-17-methylmorphinan-6-oneNot AvailableNot Available
4,5alpha-Epoxy-3-hydroxy-17-methyl-6-morphinanoneNot AvailableNot Available
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
HydromorphoneNot AvailableNot 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
EXALGONot Available
PalladoneNot Available
Brand mixturesNot Available
Categories
CAS number466-99-9
WeightAverage: 285.3377
Monoisotopic: 285.136493479
Chemical FormulaC17H19NO3
InChI KeyWVLOADHCBXTIJK-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
Not Available
Dihydroisomorphine-6-glucuronideDetails
Hydromorphone
Not Available
Hydromorphone-3-glucosideDetails
Hydromorphone
Not Available
Hydromorphone-3-glucuronideDetails
Hydromorphone
Not Available
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.

Targets

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

Enzymes

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

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