U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C18H23NO3.C4H6O6
Molecular Weight 451.467
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIHYDROCODEINE BITARTRATE

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.[H][C@@]12OC3=C4C(C[C@H]5N(C)CC[C@@]14[C@@]5([H])CC[C@@H]2O)=CC=C3OC

InChI

InChIKey=ZGSZBVAEVPSPFM-HYTSPMEMSA-N
InChI=1S/C18H23NO3.C4H6O6/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19;5-1(3(7)8)2(6)4(9)10/h3,6,11-13,17,20H,4-5,7-9H2,1-2H3;1-2,5-6H,(H,7,8)(H,9,10)/t11-,12+,13-,17-,18-;1-,2-/m01/s1

HIDE SMILES / InChI

Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C18H23NO3
Molecular Weight 301.3801
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including

Dihydrocodeine is an opioid analgesic used as an alternative or adjunct to codeine to treat moderate to severe pain, severe dyspnea, and cough. It is semi-synthetic, and was developed in Germany in 1908 during an international search to find a more effective antitussive agent to help reduce the spread of airborne infectious diseases such as tuburculosis. It was marketed in 1911. Dihydrocodeine is metabolized to dihydromorphine -- a highly active metabolite with a high affinity for mu opioid receptors. Dihydrocodeine is used for the treatment of moderate to severe pain, including post-operative and dental pain. It can also be used to treat chronic pain, breathlessness and coughing. In heroin addicts, dihydrocodeine has been used as a substitute drug, in doses up to 2500mg/day to treat addiction.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.3 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
SYNALGOS-DC

Approved Use

For the relief of moderate to moderately severe pain.

Launch Date

-3.62620813E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
487 pmol/g
60 mg 2 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
341 nM
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
739 nM
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
918 nM
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
60.089 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
18 nM
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8.7 nM
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
4.7 pmol/g
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
13 nM
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3367 nM × h
60 mg 2 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
3415 nM × h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
5118 nM × h
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
6566 nM × h
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
301.643 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
132 nM × h
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
65 nM × h
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
70 nM × h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
99 nM × h
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.146 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
32 mg 6 times / day multiple, oral
Recommended
Dose: 32 mg, 6 times / day
Route: oral
Route: multiple
Dose: 32 mg, 6 times / day
Co-administed with::
aspirin(356.4 mg)
caffeine(30 mg)
Sources:
unhealthy, > 18 years
Health Status: unhealthy
Age Group: > 18 years
Sources:
Other AEs: Respiratory depression...
Other AEs:
Respiratory depression (grade 5)
Sources:
240 mg 2 times / day multiple, oral
Overdose
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Other AEs: Hypercapnic respiratory failure...
Other AEs:
Hypercapnic respiratory failure
Sources:
AEs

AEs

AESignificanceDosePopulation
Respiratory depression grade 5
32 mg 6 times / day multiple, oral
Recommended
Dose: 32 mg, 6 times / day
Route: oral
Route: multiple
Dose: 32 mg, 6 times / day
Co-administed with::
aspirin(356.4 mg)
caffeine(30 mg)
Sources:
unhealthy, > 18 years
Health Status: unhealthy
Age Group: > 18 years
Sources:
Hypercapnic respiratory failure
240 mg 2 times / day multiple, oral
Overdose
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
PubMed

PubMed

TitleDatePubMed
ECG abnormalities in co-proxamol (paracetamol/dextropropoxyphene) poisoning.
2005
Simultaneous analysis of thebaine, 6-MAM and six abused opiates in postmortem fluids and tissues using Zymark automated solid-phase extraction and gas chromatography-mass spectrometry.
2005 Aug 5
Clinical urinalysis of drugs and alcohol in instances of suspected surreptitious administration ("spiked drinks").
2005 Jul-Sep
The effect of non-steroidal anti-inflammatory drugs on medical abortion with mifepristone and misoprostol at 13-22 weeks gestation.
2005 Nov
Evaluation of buprenorphine CEDIA assay versus GC-MS and ELISA using urine samples from patients in substitution treatment.
2005 Nov-Dec
Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network.
2005 Sep
Palliative management of refractory dyspnea in COPD.
2006
Hyperinflation and its management in COPD.
2006
Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners.
2006 Aug 15
Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: A randomized controlled trial.
2006 Dec
Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass Spectrometry.
2006 Dec 1
Simple and sensitive determination of free and total morphine in human liver and kidney using gas chromatography-mass spectrometry.
2006 Jan 18
Treatment of pain during medical abortion.
2006 Jul
Transdermal buprenorphine in the management of persistent pain - safety aspects.
2006 Mar
Validation of the Immunalysis microplate ELISA for the detection of buprenorphine and its metabolite norbuprenorphine in urine.
2006 Mar
Comparison of an automated and point-of-care immunoassay to GC-MS for urine oxycodone testing in the clinical laboratory.
2006 Mar
Substance abuse in pregnancy: opioid substitution in a northern Ireland maternity unit.
2006 Sep
Review of deaths related to analgesic- and cough suppressant-opioids; England and Wales 1996-2002.
2006 Sep
An exploratory study in the UK of the effectiveness of three different pain management regimens for post-caesarean section women.
2006 Sep
Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer.
2006 Sep 30
Glucuronidation of paracetamol by human liver microsomes in vitro / enzyme kinetic parameters and interactions with short-chain aliphatic alcohols and opiates.
2007
[Transient sick sinus syndrome by oral intake of high dose dehydrocodeine for postherpetic neuralgia].
2007 Apr
Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning.
2007 Apr
Dihydrocodeine as effective as methadone for maintenance of treatment for opiate dependence?
2007 Aug
Deglutition and respiration: development, coordination, and practical implications.
2007 Aug
Distribution of drugs of abuse within specific regions of the human brain.
2007 Aug 6
Patterns in drug use in the United Kingdom as revealed through analysis of hair in a large population sample.
2007 Aug 6
London audit of drug-related overdose deaths: characteristics and typology, and implications for prevention and monitoring.
2007 Feb
Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions.
2007 Feb 15
Substitution treatment for opioid addicts in Germany.
2007 Feb 2
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.
2007 Jan 8
Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial.
2007 Jan 8
A mixed methods study to investigate needs assessment for knee pain and disability: population and individual perspectives.
2007 Jul 4
Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs.
2007 Jul 9
The enantiomers of tramadol and its major metabolite inhibit peristalsis in the guinea pig small intestine via differential mechanisms.
2007 Mar 16
"Me's me and you's you": Exploring patients' perspectives of single patient (n-of-1) trials in the UK.
2007 Mar 19
Pharmacokinetic-pharmacodynamic modeling of the miotic effects of dihydrocodeine in humans.
2007 Nov
The role of tramadol in current treatment strategies for musculoskeletal pain.
2007 Oct
The effect of ethanol on the release of opioids from oral prolonged-release preparations.
2007 Oct
Factors that help injecting drug users to access and benefit from services: A qualitative study.
2007 Oct 30
Hemodynamic effects of methadone and dihydrocodeine in overdose.
2007 Oct-Nov
Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry.
2007 Sep
Development and GC-MS validation of a highly sensitive recombinant G6PDH-based homogeneous immunoassay for the detection of buprenorphine and norbuprenorphine in urine.
2007 Sep
The management of dyspnea in cancer patients: a systematic review.
2008 Apr
Resolution of secondary amenorrhoea following withdrawal of dihydocodeine.
2008 Apr
Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.
2008 Apr 11
[Liposomal boron delivery system for neutron capture therapy].
2008 Feb
Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study.
2008 Jan 26
Differentiation between drug use and environmental contamination when testing for drugs in hair.
2008 Mar 21
Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002-2005.
2008 May 6
Patents

Sample Use Guides

The usual dose of dihydrocodeine is 1 tablet every 4 to 6 hours
Route of Administration: Oral
Dihydrocodeine inhibited paracetamol glucuronidation with Ki value 4.02 mmol/l in human liver microsomes
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:00:15 UTC 2023
Edited
by admin
on Fri Dec 15 16:00:15 UTC 2023
Record UNII
8LXS95BSA9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIHYDROCODEINE BITARTRATE
ORANGE BOOK   USP   VANDF   WHO-DD  
Common Name English
DIHYDROCODEINE TARTRATE
MART.   MI  
Common Name English
DIHYDROCODEINE HYDROGEN TARTRATE [EP MONOGRAPH]
Common Name English
DIHYDROCODEINE BITARTRATE [USP MONOGRAPH]
Common Name English
DIHYDROCODEINE BITARTRATE [VANDF]
Common Name English
DF 118
Code English
TREZIX COMPONENT DIHYDROCODEINE BITARTRATE
Brand Name English
SYNALGOS-DC-A COMPONENT DIHYDROCODEINE BITARTRATE
Common Name English
DIHYDROCODEINE TARTRATE [MI]
Common Name English
DIHYDROCODEINE TARTRATE [MART.]
Common Name English
4,5.ALPHA.-EPOXY-3-METHOXY-17-METHYLMORPHINAN-6A-OL (+)-TARTRATE (SALT)
Common Name English
DIHYDROCODEINE BITARTRATE COMPONENT OF SYNALGOS-DC
Common Name English
SYNALGOS-DC COMPONENT DIHYDROCODEINE BITARTRATE
Common Name English
DIHYDROCODEINE BITARTRATE CII
USP-RS  
Common Name English
Dihydrocodeine bitartrate [WHO-DD]
Common Name English
DIHYDROCODEINE BITARTRATE COMPONENT OF DHC PLUS
Common Name English
DIHYDROCODEINE BITARTRATE [ORANGE BOOK]
Common Name English
DHC PLUS COMPONENT DIHYDROCODEINE BITARTRATE
Common Name English
DIHYDROCODEINE BITARTRATE [USP-RS]
Common Name English
MORPHINAN-6-OL, 4,5-EPOXY-3-METHOXY-17-METHYL-, (5.ALPHA.,6.ALPHA.)-2,3-DIHYDROXYBUTANEDIOATE (1:1) (SALT)
Common Name English
NSC-117857
Code English
CODEINE, DIHYDRO-, TARTRATE (1:1)
Common Name English
DIHYDROCODEINE BITARTRATE COMPONENT OF SYNALGOS-DC-A
Common Name English
DIHYDROCODEINE HYDROGEN TARTRATE
EP  
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67413
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
NCI_THESAURUS C1506
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
DEA NO. 9120
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
Code System Code Type Description
SMS_ID
100000078009
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
NCI_THESAURUS
C47490
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
DAILYMED
8LXS95BSA9
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
RS_ITEM_NUM
1200804
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
CAS
5965-13-9
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
EPA CompTox
DTXSID00975047
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
PUBCHEM
5492624
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
ECHA (EC/EINECS)
227-747-7
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
FDA UNII
8LXS95BSA9
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
EVMPD
SUB01704MIG
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
DRUG BANK
DBSALT000048
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
RXCUI
104966
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY RxNorm
MERCK INDEX
m4459
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY Merck Index
ChEMBL
CHEMBL1595
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
NSC
117857
Created by admin on Fri Dec 15 16:00:15 UTC 2023 , Edited by admin on Fri Dec 15 16:00:15 UTC 2023
PRIMARY
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