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

Details

Stereochemistry ABSOLUTE
Molecular Formula 2C18H21NO3.3H2O.2H3O4P
Molecular Weight 848.7647
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CODEINE PHOSPHATE SESQUIHYDRATE

SMILES

O.O.O.OP(O)(O)=O.OP(O)(O)=O.COC1=CC=C2C[C@@H]3[C@@H]4C=C[C@H](O)[C@@H]5OC1=C2[C@]45CCN3C.COC6=CC=C7C[C@@H]8[C@@H]9C=C[C@H](O)[C@@H]%10OC6=C7[C@]9%10CCN8C

InChI

InChIKey=UDIMULCGRYVAIM-REWFBLHLSA-N
InChI=1S/2C18H21NO3.2H3O4P.3H2O/c2*1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19;2*1-5(2,3)4;;;/h2*3-6,11-13,17,20H,7-9H2,1-2H3;2*(H3,1,2,3,4);3*1H2/t2*11-,12+,13-,17-,18-;;;;;/m00...../s1

HIDE SMILES / InChI

Molecular Formula H3O4P
Molecular Weight 97.9952
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C18H21NO3
Molecular Weight 299.3642
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
6.1 µM [EC50]
Target ID: P41145
Gene ID: 4986.0
Gene Symbol: OPRK1
Target Organism: Homo sapiens (Human)
Target ID: P41143
Gene ID: 4985.0
Gene Symbol: OPRD1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CAPITAL AND CODEINE

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
66.9 ng/mL
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
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
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
0.61 μM × h
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
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
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.47 h
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
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
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
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
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
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
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
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
75%
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

Doses

DosePopulationAdverse 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:
unhealthy
Health Status: unhealthy
Sex: M+F
Food Status: UNKNOWN
Sources:
OverviewDrug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
LC method for the analysis of paracetamol, caffeine and codeine phosphate in pharmaceutical preparations.
2001-12
The role of adrenal corticosteroids in induction of micronuclei by morphine.
2001-11-15
Nutritional effects of surgical and medical treatment for short bowel syndrome.
2001-11-02
Scalp nerve blocks decrease the severity of pain after craniotomy.
2001-11
Concentration ratios of morphine to codeine in blood of impaired drivers as evidence of heroin use and not medication with codeine.
2001-11
Endogenous morphine and codeine. Possible role as endogenous anticonvulsants.
2001-10-12
Drug contamination of US paper currency.
2001-10-01
Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients.
2001-10-01
Novel dynamic polymer coating for capillary electrophoresis in nonaqueous methanolic background electrolytes.
2001-10
Seizures with intravenous codeine phosphate.
2001-10
Incorporation of selegiline metabolites into hair after oral selegiline intake.
2001-10
Analysis of morphine and codeine in samples adulterated with Stealth.
2001-10
Detection of opiate use in a methadone maintenance treatment population with the CEDIA 6-acetylmorphine and CEDIA DAU opiate assays.
2001-10
Ropivacaine with or without clonidine improves pediatric tonsillectomy pain.
2001-10
Experience with urine drug testing by the Correctional Service of Canada.
2001-09-15
Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999.
2001-09
Community pharmacists' experience of over-the-counter medicine misuse in Scotland.
2001-09
Cetirizine inhibits skin reactions but not mediator release in immediate and developing late-phase allergic cutaneous reactions. A double-blind, placebo-controlled study.
2001-09
Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.
2001-09
Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial.
2001-09
Blind trials of an onsite saliva drug test for marijuana and opiates.
2001-09
[Weak opioids].
2001-09
[Strong opioids].
2001-09
Concentration ratios of codeine-to-morphine in plasma after a single oral dose (100 mg) of codeine phosphate.
2001-09
Detection of non-prescription heroin markers in urine with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
2001-09
Pain control in medical abortion.
2001-09
Engineering novel biocatalytic routes for production of semisynthetic opiate drugs.
2001-09
Can standard open pediatric urological procedures be performed on an outpatient basis?
2001-09
Precipitated withdrawal following codeine administration is dependent on CYP genotype.
2001-08-17
From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial.
2001-08-15
Heroin use by motorists in Sweden confirmed by analysis of 6-acetylmorphine in urine.
2001-08-14
Laboratory analysis of remotely collected oral fluid specimens for opiates by immunoassay.
2001-08-14
Prescribing limitations.
2001-08-11
[Paracetamol-codeine induced hepatic colic].
2001-08-02
Randomized placebo controlled trial of lofexidine hydrochloride for chronic pelvic pain in women.
2001-08
Simultaneous determination of codeine and ethyl morphine HCL in tablet formulations using LC.
2001-08
Sticky business: patterns of procurement and misuse of prescription cough syrup in Houston.
2001-07-31
Head-column field-amplified sample stacking in presence of siphoning. Application to capillary electrophoresis-electrospray ionization mass spectrometry of opioids in urine.
2001-07-27
Use of beta-cyclodextrin in the capillary zone electrophoretic separation of the components of clandestine heroin preparations.
2001-07-27
Opiate-sensitivity: clinical characteristics and the role of skin prick testing.
2001-07
Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK-PD modelling analysis.
2001-07
[Information on preparations containing codeine].
2001-06-20
[Chronic pain in geriatrics].
2001-06
Effect of apical trephination on postoperative pain and swelling in symptomatic necrotic teeth.
2001-06
Codeine phosphate in paediatric medicine.
2001-03
Codeine phosphate in children: time for re-evaluation?
2001-03
Effect of penicillin on postoperative endodontic pain and swelling in symptomatic necrotic teeth.
2001-02
Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic teeth.
2001-01
Over-the-counter medications for acute cough in children and adults in ambulatory settings.
2001
Dystonia as acute adverse reaction to cough suppressant in a 3-year-old girl.
2001
Patents

Sample Use Guides

Unknown
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Mon Mar 31 19:08:32 GMT 2025
Edited
by admin
on Mon Mar 31 19:08:32 GMT 2025
Record UNII
BKA0632GWS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CODEINE PHOSPHATE SESQUIHYDRATE
EP   WHO-DD   WHO-IP  
Common Name English
7,8-DIDEHYDRO-4,5.ALPHA.-EPOXY-3-METHOXY-17-METHYLMORPHINAN-6.ALPHA.-OL PHOSPHATE SESQUIHYDRATE
Preferred Name English
CODEINE PHOSPHATE SESQUIHYDRATE [EP MONOGRAPH]
Common Name English
Codeine phosphate sesquihydrate [WHO-DD]
Common Name English
CODEINE PHOSPHATE SESQUIHYDRATE [WHO-IP]
Common Name English
Code System Code Type Description
CAS
5913-76-8
Created by admin on Mon Mar 31 19:08:32 GMT 2025 , Edited by admin on Mon Mar 31 19:08:32 GMT 2025
PRIMARY
FDA UNII
BKA0632GWS
Created by admin on Mon Mar 31 19:08:32 GMT 2025 , Edited by admin on Mon Mar 31 19:08:32 GMT 2025
PRIMARY
EPA CompTox
DTXSID20207872
Created by admin on Mon Mar 31 19:08:32 GMT 2025 , Edited by admin on Mon Mar 31 19:08:32 GMT 2025
PRIMARY
SMS_ID
100000092021
Created by admin on Mon Mar 31 19:08:32 GMT 2025 , Edited by admin on Mon Mar 31 19:08:32 GMT 2025
PRIMARY
PUBCHEM
5492885
Created by admin on Mon Mar 31 19:08:32 GMT 2025 , Edited by admin on Mon Mar 31 19:08:32 GMT 2025
PRIMARY
EVMPD
SUB01408MIG
Created by admin on Mon Mar 31 19:08:32 GMT 2025 , Edited by admin on Mon Mar 31 19:08:32 GMT 2025
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
CODEINE PHOSPHATE SESQUIHYDRATE
Created by admin on Mon Mar 31 19:08:32 GMT 2025 , Edited by admin on Mon Mar 31 19:08:32 GMT 2025
PRIMARY Description: Small, colourless crystals or a white, crystalline powder; odourless.Solubility: Soluble in 4 parts of water; slightly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R.Category: Antitussive; analgesic.Storage: Codeine phosphate should be kept in a tightly closed container, protected from light.Labelling: The designation on the container should state if the Codeine phosphate is the hemihydrate or the sesquihydrate.Additional information: Codeine phosphate effloresces in dry air.
Related Record Type Details
PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
Pending
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
correction factor: for the calculation of content, multiply the peak area of impurity C by 0.25
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY