CODEINE ANHYDROUS

US Approved OTC

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H21NO3
Molecular Weight	299.3642
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=OROGSEYTTFOCAN-DNJOTXNNSA-N

InChI=1S/C18H21NO3/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/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://online.lexi.com/lco/medguides/622452.pdf | https://www.ncbi.nlm.nih.gov/pubmed/7885194

Codeine is an opiate used to manage mild to moderate pain severe enough to require an opioid. Codeine is a selective agonist for the mu opioid receptor and has an affinity to delta and kappa-opioid receptors. In some countries, this drug is regulated under various narcotic control laws, because its chronic use can cause physical dependence. In others, it is available without a medical prescription in combination with paracetamol.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
Mu opioid receptor 231 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7885194 \| \|https://adisinsight.springer.com/drugs/800042774	Agonist 2752	6.1 µM [EC50]
Kappa-type opioid receptor 61 Target ID: P41145 Gene ID: 4986.0 Gene Symbol: OPRK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7885194	Agonist 2752
Delta-type opioid receptor 46 Target ID: P41143 Gene ID: 4985.0 Gene Symbol: OPRD1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7885194	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: https://online.lexi.com/lco/medguides/622452.pdf	Primary		Approved 8583	CAPITAL AND CODEINE Approved Use Unknown

C_max

Value	Dose	Analyte	Population
66.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
145 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
229 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, intramuscular dose: 60 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
93 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
242 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, intramuscular dose: 60 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
53.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MORPHINE-3-GLUCURONIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
66.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
968 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE-6-GLUCURONIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
0.61 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
466 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
849 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, intramuscular dose: 60 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
467 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
937 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, intramuscular dose: 60 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.47 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, intramuscular dose: 60 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7094509/	60 mg single, intramuscular dose: 60 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.71 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MORPHINE-3-GLUCURONIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.47 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.75 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1391681/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	CODEINE-6-GLUCURONIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
75% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022402s000lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		CODEINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
360 mg 1 times / day multiple, oral Highest recorded dose Dose: 360 mg, 1 times / day Route: oral Route: multiple Dose: 360 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022402s000lbl.pdf	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022402s000lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022402s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 620 UGT2B7 197 CYP19A1 429 CYP1A2 2153	UGT2B7 456 UGT1A3 470 UGT1A1 479 UGT1A4 399 OCT1 393 UGT2B4 278 UGT1A8 323 UGT1A10 331 P-gp 2052 UGT2B15 236

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671196#sid=144207280	inconclusive [IC50 35.7774 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144207280	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671199#sid=144207280	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671198#sid=144207280	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671201#sid=144207280	no
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15781124/	unlikely [IC50 400 uM]
OCT1 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23835420/	yes [IC50 10.5 uM]

Drug as victim

Target	Modality	Activity	Metabolite
UGT2B4 278	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022402s014lbl.pdf#pag3=24 Page: 24.0	major
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022402s000_PharmR.pdf#page=20 Page: 20.0	major
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18311899/	no
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022402s000_PharmR.pdf#page=20 Page: 20.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022402s000_PharmR.pdf#page=20 Page: 20.0	yes
OCT1 393	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23835420/	yes
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24458010/	yes	Morphine 12
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24458010/	yes	Morphine 12

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/19034038/

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1Q4DTD
Alfa Chemistry	170301
Alfa Chemistry	ACM52453040
AN PharmaTech	AN-23899
Angene	AGN-PC-0U9ZUU
Aurora Fine Chemicals LLC	A17.876.233	http://online.aurorafinechemicals.com/info?ID=A17.876.233
Avantor Inc	75835-236	https://us.vwr.com/store/product/21998648/exempted-drug-of-abuse-reference-standards-restek
Changzhou Highassay Chemical Co., Ltd	my_sub1415
Chemieliva Pharmaceutical Co., Ltd	PBCM0821173
ChemMol	30101025	http://www.chemmol.com/chemmol/30101025.html
ChemMol	49416695	http://www.chemmol.com/chemmol/49416695.html
ChemMol	99138769	http://www.chemmol.com/chemmol/99138769.html
Clearsynth	CS-T-56966	http://www.clearsynth.com/en/CST56966.html
Compound Cloud	21155870
Compound Cloud	24892867
Compound Cloud	5284371
Compound Cloud	5362471
Compound Cloud	6321303
eMolecules	193733897
Hangzhou APIChem Technology	AC-11114
HongKong Chemhere	SCA54117
IBScreen	BB_NC-00138
IBScreen	STOCK1N-42851
LGC Standards	LGCAMP0004.10-01	https://www.lgcstandards.com/US/en/p/LGCAMP0004.10-01
LGC Standards	LGCAMP0004.10-02	https://www.lgcstandards.com/US/en/p/LGCAMP0004.10-02
LGC Standards	LGCFOR0004.10	https://www.lgcstandards.com/US/en/p/LGCFOR0004.10
LGC Standards	MM0004.10	https://www.lgcstandards.com/US/en/p/MM0004.10
mcule	MCULE-4129237460
mcule	MCULE-6243921692
Parchem	87121	https://www.parchem.com/chemical-supplier-distributor/Codeine-Alkaloid-087121.aspx
Parchem	87123	https://www.parchem.com/chemical-supplier-distributor/Codeine-USP-087123.aspx
Sigma-Aldrich	C-006_CERILLIAN	https://www.sigmaaldrich.com/catalog/product/cerillian/c006?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	C1653_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/c1653?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	Y0000722_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/y0000722?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma Aldrich	C1653\|SIAL
Sigma Aldrich	C3539\|SIAL
Sigma Aldrich	C5901\|SIAL
Sigma Aldrich	Y0000722
Sigma Aldrich	Y0000722\|SIAL
Smolecule	S627560	https://www.smolecule.com/products/s627560
Tetrahedron	TS63993
Tetrahedron	TS80953
Toronto Research Chemicals	C634075
Toronto Research Chemicals	C634080
Toronto Research Chemicals	KIT0410
Toronto Research Chemicals	KIT2460
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-1498A
ZINC	ZINC000003806721	http://zinc15.docking.org/substances/ZINC000003806721

PubMed

Title	Date	PubMed
Mimicking gene defects to treat drug dependence.	2000	10911933
Codeine analgesia is due to codeine-6-glucuronide, not morphine.	2000 Jul-Aug	11092114
Over-the-counter medications for acute cough in children and adults in ambulatory settings.	2001	11686998
Dystonia as acute adverse reaction to cough suppressant in a 3-year-old girl.	2001	11587381
[Guillain-Barre syndrome as a result of poisoning with a mixture of "kompot"(Polish heroin) and drugs].	2001	11450369
Determination of opiates in serum, saliva and hair addicted persons.	2001	11450354
Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.	2001	11438043
The use of compound 48/80 and codeine phosphate as positive controls for intradermal skin testing in dogs.	2001 Apr	11360343
Chromatographic analysis of phenethylamine-antihistamine combinations using C8, C18 or cyano columns and micellar sodium dodecyl sulfate-pentanol mixtures.	2001 Apr	11340978
Angle closure risk from proprietary medicines.	2001 Apr	11339612
[Adverse cutaneous side-effect of codeine administration].	2001 Apr 15	11334589
Prescribing limitations.	2001 Aug 11	11523877
Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic teeth.	2001 Jan	11487166
Packaging of codeine phosphate suppositories.	2001 Jan	11123747
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.	2001 Jan 10	11231885
Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.	2001 Jul 7	11440935
Time of drug elimination in chronic drug abusers. Case study of 52 patients in a "low-step" detoxification ward.	2001 Jun 15	11376991
Codeine phosphate in paediatric medicine.	2001 Mar	11573533
Myocardial Infarction associated with methadone and/or dihydrocodeine.	2001 Mar	11316924
Acetylcodeine as a marker of illicit heroin in human hair: method validation and results of a pilot study.	2001 Mar	11300501
Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers taking codeine.	2001 May	11328255
The analgesic effect of codeine as compared to imipramine in different human experimental pain models.	2001 May	11323149
[Analgesics-induced chronic renal failure in patients on dialysis therapy in Hungary].	2001 May 13	11419294
Capillary electrophoresis-electrospray ionization ion trap mass spectrometry for analysis and confirmation testing of morphine and related compounds in urine.	2001 May 4	11382295
Regional block and mexiletine: the effect on pain after cancer breast surgery.	2001 May-Jun	11359221
Nutritional effects of surgical and medical treatment for short bowel syndrome.	2001 Nov-Dec	11688937
Novel dynamic polymer coating for capillary electrophoresis in nonaqueous methanolic background electrolytes.	2001 Oct	11699922
Ropivacaine with or without clonidine improves pediatric tonsillectomy pain.	2001 Oct	11587610
Drug contamination of US paper currency.	2001 Oct 1	11566423
Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999.	2001 Sep	11699619
Community pharmacists' experience of over-the-counter medicine misuse in Scotland.	2001 Sep	11688306
Cetirizine inhibits skin reactions but not mediator release in immediate and developing late-phase allergic cutaneous reactions. A double-blind, placebo-controlled study.	2001 Sep	11591187
Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.	2001 Sep	11589259
Blind trials of an onsite saliva drug test for marijuana and opiates.	2001 Sep	11569567

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Oral

Name

Type

Language

IDS-NC-005(SECT.-2)

Preferred Name

English

CODEINE ANHYDROUS

Common Name

English

MYTUSSIN

Common Name

English

ETHYLMORPHINE HYDROCHLORIDE IMPURITY C [EP IMPURITY]

Common Name

English

CODEINE [HSDB]

Common Name

English

CODEINE [MI]

Common Name

English

SS85U8K5ZN

Common Name

English

KODELAK FITO

Common Name

English

MORPHINE MONOMETHYL ETHER

Common Name

English

HYDROCODONE HYDROGEN TARTRATE 2.5-HYDRATE IMPURITY C [EP IMPURITY]

Common Name

English

7,8-didehydro-4,5?-epoxy-3-methoxy-17-methylmorphinan-6?-ol

Systematic Name

English

O3-METHYLMORPHINE

Common Name

English

CODICEPT

Common Name

English

DIHYDROCODEINE HYDROGEN TARTRATE IMPURITY A [EP IMPURITY]

Common Name

English

Codeine [WHO-DD]

Common Name

English

METHYLMORPHINE

Common Name

English

CODUCEPT

Common Name

English

MORPHINAN-6-OL, 7,8-DIDEHYDRO-4,5-EPOXY-3-METHOXY-17-METHYL-, (5.ALPHA.,6.ALPHA.)-

Systematic Name

English

MORPHINE SULFATE IMPURITY A [EP IMPURITY]

Common Name

English

MORPHINE HYDROCHLORIDE IMPURITY A [EP IMPURITY]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175690