DIHYDROCODEINE BITARTRATE

US Previously Marketed

First approved in 1956

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 Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.COC1=C2O[C@H]3[C@@H](O)CC[C@H]4[C@H]5CC(C=C1)=C2[C@@]34CCN5C

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
Sources: http://www.drugbank.ca/drugs/DB01551
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 231 Target ID: CHEMBL233 Sources: http://www.genome.jp/dbget-bin/www_bget?D07831	Agonist 2752		0.3 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/011483s027lbl.pdf	Palliative		Approved 8583	SYNALGOS-DC Approved Use For the relief of moderate to moderately severe pain. Launch Date 1958

C_max

Value	Dose	Analyte	Population
487 pmol/g EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
4.7 pmol/g EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
341 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
8.7 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
739 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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 EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
18 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
13 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
60.089 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885392/	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

AUC

Value	Dose	Analyte	Population
3367 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
70 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
3415 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
65 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
5118 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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 EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
132 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
99 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
301.643 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885392/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.146 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885392/	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

Dose	Population	Adverse 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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf	unhealthy, > 18 years Health Status: unhealthy Age Group: > 18 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf	Other AEs: Respiratory depression... Other AEs: Respiratory depression (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/26479786	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/26479786	Other AEs: Hypercapnic respiratory failure... Other AEs: Hypercapnic respiratory failure Sources: https://pubmed.ncbi.nlm.nih.gov/26479786

AEs

AE	Significance	Dose	Population
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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf	unhealthy, > 18 years Health Status: unhealthy Age Group: > 18 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/26479786	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/26479786

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1197 CYP2A6 626 CYP2C19 1119 UGT2B7 456

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2A6 626	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2C19 1119	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2C9 1193	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2D6 1388	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/14597688/ Page: 3.0	yes
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/14597688/ Page: 3.0	yes

Sourcing

Vendor/Aggregator	ID	URL
BioSynth	D-3270
Compound Cloud	46174078
Compound Cloud	5284543
Compound Cloud	5492624
Compound Cloud	5493302
eMolecules	303498464
NovoSeek	5284543
Parchem	56756	https://www.parchem.com/chemical-supplier-distributor/Pseudomorphine-056756.aspx
Sigma Aldrich	D-019
Sigma Aldrich	D-019\|CERILLIAN
Smolecule	S526105	http://www.smolecule.com/products/s526105
Tetrahedron	TS81021
THE BioTek	bt-264832	https://www.thebiotek.com/product/inhibitors/bt-264832
Toronto Research Chemicals	KIT2290
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-0343A
ZINC	ZINC000004215736	http://zinc15.docking.org/substances/ZINC000004215736

PubMed

Title	Date	PubMed
Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002-2005.	2008-05-06	18460194
Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.	2008-04-11	18405372
The management of dyspnea in cancer patients: a systematic review.	2008-04	18214551
Resolution of secondary amenorrhoea following withdrawal of dihydocodeine.	2008-04	17973946
Differentiation between drug use and environmental contamination when testing for drugs in hair.	2008-03-21	17980987
[Liposomal boron delivery system for neutron capture therapy].	2008-02	18239367
Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study.	2008-01-26	18182416
Pharmacokinetic-pharmacodynamic modeling of the miotic effects of dihydrocodeine in humans.	2007-11	17786418
Factors that help injecting drug users to access and benefit from services: A qualitative study.	2007-10-30	17971204
The role of tramadol in current treatment strategies for musculoskeletal pain.	2007-10	18472996
The effect of ethanol on the release of opioids from oral prolonged-release preparations.	2007-10	17882730
Hemodynamic effects of methadone and dihydrocodeine in overdose.	2007-09-14	17852162
Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry.	2007-09	17725888
Development and GC-MS validation of a highly sensitive recombinant G6PDH-based homogeneous immunoassay for the detection of buprenorphine and norbuprenorphine in urine.	2007-09	17725885
Distribution of drugs of abuse within specific regions of the human brain.	2007-08-06	17629644
Patterns in drug use in the United Kingdom as revealed through analysis of hair in a large population sample.	2007-08-06	17614228
Dihydrocodeine as effective as methadone for maintenance of treatment for opiate dependence?	2007-08	17652570
Deglutition and respiration: development, coordination, and practical implications.	2007-08	17647129
Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs.	2007-07-09	17620111
A mixed methods study to investigate needs assessment for knee pain and disability: population and individual perspectives.	2007-07-04	17610732
[Transient sick sinus syndrome by oral intake of high dose dehydrocodeine for postherpetic neuralgia].	2007-04	17441449
Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning.	2007-04	17407385
"Me's me and you's you": Exploring patients' perspectives of single patient (n-of-1) trials in the UK.	2007-03-19	17371593
The enantiomers of tramadol and its major metabolite inhibit peristalsis in the guinea pig small intestine via differential mechanisms.	2007-03-16	17367519
Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions.	2007-02-15	17178092
Substitution treatment for opioid addicts in Germany.	2007-02-02	17270059
London audit of drug-related overdose deaths: characteristics and typology, and implications for prevention and monitoring.	2007-02	17222287
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.	2007-01-08	17210080
Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial.	2007-01-08	17210079
Glucuronidation of paracetamol by human liver microsomes in vitro / enzyme kinetic parameters and interactions with short-chain aliphatic alcohols and opiates.	2007	18380412
Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass Spectrometry.	2006-12-01	17180984
Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: A randomized controlled trial.	2006-12	17156174
Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer.	2006-09-30	16631290
Substance abuse in pregnancy: opioid substitution in a northern Ireland maternity unit.	2006-09	16964809
Review of deaths related to analgesic- and cough suppressant-opioids; England and Wales 1996-2002.	2006-09	16944410
An exploratory study in the UK of the effectiveness of three different pain management regimens for post-caesarean section women.	2006-09	16356609
Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners.	2006-08-15	16777416
Treatment of pain during medical abortion.	2006-07	16781260
Transdermal buprenorphine in the management of persistent pain - safety aspects.	2006-03	18360586
Validation of the Immunalysis microplate ELISA for the detection of buprenorphine and its metabolite norbuprenorphine in urine.	2006-03	16620543
Comparison of an automated and point-of-care immunoassay to GC-MS for urine oxycodone testing in the clinical laboratory.	2006-03	16620541
Clinical urinalysis of drugs and alcohol in instances of suspected surreptitious administration ("spiked drinks").	2006-01-28	16438340
Simple and sensitive determination of free and total morphine in human liver and kidney using gas chromatography-mass spectrometry.	2006-01-18	16311082
Palliative management of refractory dyspnea in COPD.	2006	18046866
Hyperinflation and its management in COPD.	2006	18044095
Evaluation of buprenorphine CEDIA assay versus GC-MS and ELISA using urine samples from patients in substitution treatment.	2005-12-17	16356333
The effect of non-steroidal anti-inflammatory drugs on medical abortion with mifepristone and misoprostol at 13-22 weeks gestation.	2005-11	16055455
Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network.	2005-09	16218160
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.	2005-08-05	15993661
ECG abnormalities in co-proxamol (paracetamol/dextropropoxyphene) poisoning.	2005	16035201

Patents

Sample Use Guides

In Vivo Use Guide

The usual dose of dihydrocodeine is 1 tablet every 4 to 6 hours

Route of Administration: Oral

In Vitro Use Guide

Dihydrocodeine inhibited paracetamol glucuronidation with Ki value 4.02 mmol/l in human liver microsomes

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:15:59 GMT 2025` Edited by `admin` on `Mon Mar 31 18:15:59 GMT 2025`
Record UNII	8LXS95BSA9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DIHYDROCODEINE TARTRATE

Preferred Name

English

DIHYDROCODEINE BITARTRATE

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

SYNALGOS-DC COMPONENT DIHYDROCODEINE BITARTRATE

Common Name

English

DIHYDROCODEINE BITARTRATE CII

Common Name

English

Dihydrocodeine bitartrate [WHO-DD]

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 HYDROGEN TARTRATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67413