Identification

Name
Codeine
Accession Number
DB00318  (APRD00120, DB09471)
Type
Small Molecule
Groups
Approved, Illicit
Description

An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough.

Structure
Thumb
Synonyms
  • (−)-Codeine
  • (5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
  • (5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
  • 3-Methylmorphin
  • 3-methylmorphine
  • 7,8-didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-ol
  • 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol
  • Codein
  • Codeína
  • Codéine
  • Codeine anhydrous
  • Codeine polistirex
  • Codeinum
  • L-Codeine
  • Methylmorphine
  • morphine 3-methyl ether
  • Morphine monomethyl ether
  • morphine monomethyl ether
  • morphine-3-methyl ether
  • O(3)-methylmorphine
External IDs
IDS-NC-005(SECT.-2)
Product Ingredients
IngredientUNIICASInChI Key
Codeine hydrochloride406LPJ779Q1422-07-7NUXLENPAZQNFAM-FFHNEAJVSA-N
Codeine monohydrateQ830PW75206059-47-8WRRSFOZOETZUPG-FFHNEAJVSA-N
Codeine phosphate2X585M1M3T52-28-8WUXLCJZUUHIXFY-FFHNEAJVSA-N
Codeine phosphate hemihydrateGSL05Y1MN641444-62-6DKSZLDSPXIWGFO-BLOJGBSASA-N
Codeine sulfate11QV9BS0CB6854-40-6BOLDZXRCJAJADM-AAXBYHQXSA-N
Codeine sulfate anhydrousAVW5HY4N2E1420-53-7BCXHDORHMMZBBZ-DORFAMGDSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Codeine 15Tablet15 mgOralLaboratoire Riva Inc1994-12-31Not applicableCanada
Codeine 30Tablet30 mgOralLaboratoire Riva Inc1994-12-31Not applicableCanada
Codeine Contin 100mg Controlled Release TabTablet, extended release100 mgOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 150mg Controlled Release TabTablet, extended release150 mgOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 200mg Controlled Release TabTablet, extended release200 mgOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 50mg Controlled Release TabTablet, extended release50 mgOralPurdue Pharma1997-03-13Not applicableCanada
Codeine Phosphate Inj 30mg/mlSolution30 mgIntramuscular; SubcutaneousHospira, Inc.1981-12-31Not applicableCanada
Codeine Phosphate Inj 60mg/mlSolution60 mgIntramuscular; SubcutaneousHospira, Inc.1981-12-31Not applicableCanada
Codeine Phosphate Injection USPLiquid30 mgIntramuscular; SubcutaneousSandoz Canada Incorporated1978-12-31Not applicableCanada
Codeine Phosphate SyrupSyrup25 mgOralLaboratoire Atlas Inc1986-12-18Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Codeine SulfateTablet15 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
Codeine SulfateTablet60 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
Codeine SulfateTablet30 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
PMS-codeineTablet30 mgOralPharmascience Inc2001-12-16Not applicableCanada
PMS-codeineTablet15 mgOralPharmascience Inc2001-11-16Not applicableCanada
Ratio-codeineSyrup5 mgOralTeva1977-12-312017-05-01Canada
Teva-codeineTablet15 mgOralTeva1983-12-31Not applicableCanada
Teva-codeineTablet30 mgOralTeva1983-12-31Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
(extra Strength) Acetaminophen, Caffeine & 8mg Codeine Phosphate CapletsCodeine phosphate (8 mg) + Acetaminophen (500 mg) + Caffeine (15 mg)TabletOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1998-07-222002-07-31Canada
222 TabletsCodeine phosphate (8 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc1951-12-312015-08-17Canada
282 Mep TabCodeine phosphate (15 mg) + Acetylsalicylic acid (350 mg) + Caffeine citrate (30 mg) + Meprobamate (200 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1959-12-311998-08-14Canada
282 TabCodeine phosphate (15 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1951-12-311998-04-21Canada
282 TabletsCodeine phosphate (15 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralPendopharm Division Of De Pharmascience Inc1998-11-01Not applicableCanada
292 TabCodeine phosphate (30 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1951-12-311998-08-14Canada
292 TabletsCodeine phosphate (30 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralPendopharm Division Of De Pharmascience Inc1998-10-01Not applicableCanada
A & C Tablets With Codeine 15mgCodeine phosphate (15 mg) + Acetylsalicylic acid (375 mg) + Caffeine (15 mg)TabletOralD.C. Labs Limited1971-12-312003-07-11Canada
A & C Tablets With Codeine 30mgCodeine phosphate (30 mg) + Acetylsalicylic acid (375 mg) + Caffeine (15 mg)TabletOralD.C. Labs Limited1971-12-312003-07-11Canada
A.C. & C 8mg TabCodeine phosphate (8 mg) + Acetylsalicylic acid (375 mg) + Caffeine (15 mg)TabletOralVita Health Products Inc1970-12-31Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Acetaminophen and Codeine PhosphateCodeine phosphate hemihydrate (60 mg/1) + Acetaminophen (650 mg/1)TabletOralUAD LABORATORIES2006-11-22Not applicableUs
Acetaminophen with CodeineCodeine phosphate hemihydrate (15 mg/1) + Acetaminophen (300 mg/1)TabletOralVintage Pharmaceuticals, LLC2006-11-242006-11-24Us
AiracofCodeine phosphate hemihydrate (7.5 mg/5mL) + Diphenhydramine hydrochloride (12.5 mg/5mL) + Phenylephrine hydrochloride (7.5 mg/5mL)LiquidOralCenturion Labs2010-01-082016-05-02Us
Butalbital, Acetaminophen, Caffeine, and Codeine PhosphateCodeine phosphate hemihydrate (30 mg/1) + Acetaminophen (325 mg/1) + Butalbital (50 mg/1) + Caffeine (40 mg/1)CapsuleOralVintage Pharmaceuticals, LLC2007-01-222007-01-22Us
Butalbital, Aspirin, Caffeine and Codeine PhosphateCodeine phosphate hemihydrate (30 mg/1) + Acetylsalicylic acid (325 mg/1) + Butalbital (50 mg/1) + Caffeine (40 mg/1)CapsuleOralJerome Stevens Pharmaceuticals2007-10-25Not applicableUs
Butalbital, Aspirin, Caffeine, and Codeine PhosphateCodeine phosphate hemihydrate (30 mg/1) + Acetylsalicylic acid (325 mg/1) + Butalbital (50 mg/1) + Caffeine (40 mg/1)CapsuleOralWatson Laboratories, Inc.2007-02-172007-02-17Us
Butalbital, Aspirin, Caffeine, and Codeine PhosphateCodeine phosphate hemihydrate (30 mg/1) + Acetylsalicylic acid (325 mg/1) + Butalbital (50 mg/1) + Caffeine (40 mg/1)CapsuleOralEndo Pharmaceuticals Inc.2006-09-192006-09-19Us
Chlorpheniramine and CodeineCodeine phosphate hemihydrate (10 mg/5mL) + Chlorpheniramine maleate (2 mg/5mL)LiquidOralBreckenridge Pharmaceutical, Inc.2009-10-012011-02-28Us
Codeine Phosphate and Pseudoephedrine HydrochlorideCodeine phosphate hemihydrate (10 mg/5mL) + Pseudoephedrine hydrochloride (30 mg/5mL)SyrupOralBreckenridge Pharmaceutical, Inc.2009-12-012011-11-30Us
Codeine Phosphate GuaifenesinCodeine phosphate hemihydrate (10 mg/5mL) + Guaifenesin (200 mg/5mL)LiquidOralKylemore Pharmaceuticals, LLC2010-01-012012-11-30Us
International/Other Brands
Actacode (Sigma) / Bisoltus (Boehringer Ingelheim) / Bromophar (Qualiphar) / Bronchicum (Sanofi-Aventis) / Bronchodine (Pharmacobel) / Codant (Antigen) / Codedrill (Pierre Fabre) / Codein (Cristália) / Codeisan (Belmac) / Coderpina (Frycia Centro América) / Codicalm (Welti) / Codicept / Codinex (Pinewood) / Coducept / Cougel (Hwang's) / Coutan (Mey See) / Dinco (Center) / Farmacod (Farmacom) / Galcodine (Thornton & Ross) / Pectoral (Siphat) / Tussoret (MaxMedic)
Categories
UNII
UX6OWY2V7J
CAS number
76-57-3
Weight
Average: 299.3642
Monoisotopic: 299.152143543
Chemical Formula
C18H21NO3
InChI Key
OROGSEYTTFOCAN-DNJOTXNNSA-N
InChI
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
IUPAC Name
(1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-14-ol
SMILES
[H][C@@]12OC3=C(OC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O

Pharmacology

Indication

For treatment and management of pain (systemic). It is also used as an antidiarrheal and as a cough suppressant.

Associated Conditions
Pharmacodynamics

Codeine, an opiate agonist in the CNS, is similar to other phenanthrene derivatives such as morphine. It is selective for the mu receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine. The principle therapeutic action is analgesia. Codeine concentrations do not correlate with brain concentration or relief of pain. The minimum effective concentration is highly variable is influenced by numerous factors, including but not limited to, age, previous opioid use, age, and general medical condition. However, the effective dose for patients that have developed tolerance is significantly higher than the opioid-naive patients.

Mechanism of action

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

TargetActionsOrganism
AMu-type opioid receptor
partial agonist
Human
AKappa-type opioid receptor
partial agonist
Human
ADelta-type opioid receptor
agonist
Human
Absorption

Well absorbed following oral administration with a bioavailability of approximately 90%. Maximum plasma concentration occurs 60 minutes post-administration. Food does not effect the rate or extent of absorption of codeine.

Volume of distribution

Apparent volume of distribution = 3-6 L/kg

Protein binding

7-25% bound to plasma proteins.

Metabolism

Hepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6 to morphine. 70-80% of the dose undergoes glucuronidation to form codeine-6-glucuronide. This process is mediated by UDP-glucuronosyltransferase UGT2B7 and UGT2B4. 5-10% of the dose undergoes O-demethylation to morphine and 10% undergoes N-demethylation to form norcodeine. CYP2D6 mediates the biotransformation to morphine. CYP3A4 is the enzyme that mediates the conversion to norcodiene. Morphine and norcodeine are further metabolized and undergo glucuronidation. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Both morphine and morphine-6-glucuronide are active and have analgesic activity. Norcodiene and M3G do not have any analgesic properties.

Route of elimination

90% of the total dose of codeine is excreted through the kidneys, of which 10% is unchanged codeine.

Half life

Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours.

Clearance
Not Available
Toxicity

Respiratory depression, sedation and miosis and common symptoms of overdose. Other symptoms include nausea, vomiting, skeletal muscle flaccidity, bradycardia, hypotension, and cool, clammy skin. Apnea and death may ensue.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Codeine Action PathwayDrug action
Codeine Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*4(A;A)A Allele, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*6(-;-)T deletion, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole gene deletion, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*3Not Available2549delAEffect Directly StudiedThe presence of this polymorphism in CYP2D6 results in non-functioning enzyme variant and may be associated with reduced drug mtabolism or reduced therapeutic response when treated with codeine.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableA alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine and lack of therapeutic response from codeine.Details
Cytochrome P450 2D6CYP2D6*6(-;T) / (-;-)1707delTEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*1XNNot AvailableNormal allele duplicated.ADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*2XNNot Available2850C>T / 4180G>C  … show all ADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableG alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 results in non-functioning enzyme variant and may be associated with reduced therapeutic response when treated with codeine.Details
Cytochrome P450 2D6CYP2D6*4Not Available3877G>AEffect Directly StudiedThe presence of this polymorphism in CYP2D6 results in non-functioning enzyme variant and may be associated with reduced therapeutic response when treated with codeine.Details

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe risk or severity of adverse effects can be increased when (2-benzhydryloxyethyl)diethyl-methylammonium iodide is combined with Codeine.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Codeine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Codeine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Codeine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Codeine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Codeine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Codeine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Codeine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Codeine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbirateroneThe serum concentration of Codeine can be increased when it is combined with Abiraterone.
Food Interactions
  • Avoid alcohol.
  • Take with food, food reduces irritation.
  • To avoid constipation: increase your daily intake of fiber (beans, whole grains, vegetables).

References

Synthesis Reference

Nagaraj R. Ayyangar, Anil R. Choudhary, Uttam R. Kalkote, Vasant K. Sharma, "Process for the preparation of codeine from morphine." U.S. Patent US4764615, issued May, 1912.

US4764615
General References
  1. Schroeder K, Fahey T: Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001831. [PubMed:15495019]
  2. Vree TB, van Dongen RT, Koopman-Kimenai PM: Codeine analgesia is due to codeine-6-glucuronide, not morphine. Int J Clin Pract. 2000 Jul-Aug;54(6):395-8. [PubMed:11092114]
  3. Srinivasan V, Wielbo D, Tebbett IR: Analgesic effects of codeine-6-glucuronide after intravenous administration. Eur J Pain. 1997;1(3):185-90. [PubMed:15102399]
External Links
Human Metabolome Database
HMDB0004995
KEGG Drug
D03580
KEGG Compound
C06174
PubChem Compound
5284371
PubChem Substance
46507764
ChemSpider
4447447
BindingDB
50105098
ChEBI
16714
ChEMBL
CHEMBL485
Therapeutic Targets Database
DAP000213
PharmGKB
PA449088
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Codeine
ATC Codes
N02AA59 — Codeine, combinations excl. psycholepticsN02AA79 — Codeine, combinations with psycholepticsR05DA04 — Codeine
AHFS Codes
  • 48:08.00 — Antitussives
  • 28:08.08 — Opiate Agonists
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceDrug Biotransformation / Membrane Transport1
1CompletedBasic ScienceGenotype-related Drug Metabolism1
1CompletedTreatmentConstipation Drug Induced / Healthy Volunteers1
1CompletedTreatmentDiabetic Neuropathies / Fibromyalgia / Major Depressive Disorder (MDD) / Vasomotor Symptoms1
1CompletedTreatmentPain4
1Not Yet RecruitingBasic ScienceCodeine / Metformin / Organic Cation Transporter 11
1Unknown StatusTreatmentMechanically Ventilated Neonates / Painful Procedures in Newborns1
1, 2CompletedTreatmentSickle Cell Disorders1
2CompletedTreatmentCervical Pain1
2RecruitingTreatmentPainful musculoskeletal conditions1
2, 3CompletedTreatmentIdiopathic Intracranial Hypertension (IIH)1
3CompletedSupportive CareAnalgesia After ED Discharge for Extremity Injuries1
3CompletedTreatmentMyopia1
3CompletedTreatmentPostoperative Dental Pain1
3TerminatedTreatmentPain1
4CompletedPreventionAcellular Pertussis / Diphtheria / Healthy Volunteers / Tetanus1
4CompletedSupportive CarePain / Unspecified Adult Solid Tumor, Protocol Specific1
4CompletedTreatmentBack Pain / Osteoarthritis (OA)1
4CompletedTreatmentGastric Motility Disorder1
4CompletedTreatmentImpacted Third Molar Tooth1
4CompletedTreatmentPain1
4CompletedTreatmentPain / Tonsillitis1
4CompletedTreatmentPostcraniotomy Pain1
4CompletedTreatmentPostoperative pain1
4CompletedTreatmentTraumas1
4RecruitingTreatmentCervical Preparation / Pain / Pregnancy Termination1
4RecruitingTreatmentPostoperative pain1
4Unknown StatusTreatmentPostoperative Laminectomy Pain / Postoperative pain1
4WithdrawnBasic ScienceSickle Cell Disorders1
4WithdrawnTreatmentPain, Chronic1
Not AvailableCompletedDiagnosticGastric Emptying / Healthy Volunteers / Motility Disorders1
Not AvailableCompletedPreventionHeadaches1
Not AvailableCompletedTreatmentPain2
Not AvailableCompletedTreatmentPeriapical Abscess1
Not AvailableRecruitingTreatmentLow Back Pain (LBP)1
Not AvailableUnknown StatusTreatmentFracture Bone / Pain1

Pharmacoeconomics

Manufacturers
  • Roxane laboratories inc
Packagers
  • Actavis Group
  • Aidarex Pharmacuticals LLC
  • Amarin Pharmaceuticals
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Athlon Pharmaceuticals Inc.
  • Barr Pharmaceuticals
  • BASF Corp.
  • Blansett Pharmacal Co. Inc.
  • Blenheim Pharmacal
  • Breckenridge Pharmaceuticals
  • Bryant Ranch Prepack
  • C.O. Truxton Inc.
  • Cardinal Health
  • Carlisle Laboratories Inc.
  • Centurion Labs
  • Century Pharmaceuticals Inc.
  • Cerovene Inc.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • D.M. Graham Laboratories Inc.
  • DAVA Pharmaceuticals
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Duramed
  • Eon Labs
  • Glenmark Generics Ltd.
  • Golden State Medical Supply Inc.
  • Great Southern Laboratories
  • H and H Laboratories
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hi Tech Pharmacal Co. Inc.
  • Hospira Inc.
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Janssen-Ortho Inc.
  • Jerome Stevens Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Lannett Co. Inc.
  • Lehigh Valley Technologies Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • MCR American Pharmaceuticals Inc.
  • Medvantx Inc.
  • Mikart Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Nexgen Pharma Inc.
  • Novartis AG
  • Nucare Pharmaceuticals Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patient First Corp.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Association
  • Pharmedix
  • Pharmpak Inc.
  • Physicians Total Care Inc.
  • Poly Pharmaceuticals Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Roxane Labs
  • Sandhills Packaging Inc.
  • SJ Pharmaceuticals LLC
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stanley Pharmaceuticals Ltd.
  • Stat Rx Usa
  • Talbert Medical Management Corp.
  • Teva Pharmaceutical Industries Ltd.
  • TG United Inc.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Valeant Ltd.
  • Vascondor Inc.
  • Veratex Corp.
  • Vintage Pharmaceuticals Inc.
  • Watson Pharmaceuticals
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
SolutionOral
LiquidOral
Tablet, extended releaseOral
Tablet, extended releaseOral100 mg
Tablet, extended releaseOral150 mg
Tablet, extended releaseOral200 mg
Tablet, extended releaseOral50 mg
SolutionIntramuscular; Subcutaneous30 mg
SolutionIntramuscular; Subcutaneous60 mg
LiquidIntramuscular; Subcutaneous30 mg
SyrupOral25 mg
SyrupOral5 mg
TabletOral15 mg
TabletOral60 mg
SolutionOral15 mg/2.5mL
SolutionOral30 mg/5mL
TabletOral15 mg/1
TabletOral30 mg/1
TabletOral60 mg/1
Suspension, extended releaseOral
SyrupOral
SolutionOral10 mg
TabletOral
LiquidOral10 mg
CapsuleOral
TabletOral30 mg
ElixirOral
KitOral
SuspensionOral
Prices
Unit descriptionCostUnit
Codeine phosphate powder8.25USD g
Codeine Phosphate 30 mg/ml1.31USD ml
Codeine sulfate 60 mg tablet0.86USD tablet
Codeine sulfate 30 mg tablet0.76USD tablet
Codeine ph 30 mg/ml syringe0.54USD ml
Codeine ph 15 mg/ml syringe0.49USD ml
Codeine sulfate 15 mg tablet0.43USD tablet
Ratio-Codeine 30 mg Tablet0.09USD tablet
Ratio-Codeine 15 mg Tablet0.07USD tablet
Ratio-Codeine 5 mg/ml Syrup0.03USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8062667No2009-03-292029-03-29Us
US8790700No2007-03-152027-03-15Us
US9066942No2012-01-032032-01-03Us
US6383471No1999-04-062019-04-06Us
US6248363No1999-11-232019-11-23Us
US9107921No2012-01-032032-01-03Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)157.5 °CPhysProp
boiling point (°C)250 °C at 2.20E+01 mm HgPhysProp
water solubility9000 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.19AVDEEF,A ET AL. (1996)
logS-1.52ADME Research, USCD
pKa8.21 (at 25 °C)LIDE,DR (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.577 mg/mLALOGPS
logP1.2ALOGPS
logP1.34ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)13.78ChemAxon
pKa (Strongest Basic)9.19ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.93 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity84.6 m3·mol-1ChemAxon
Polarizability31.95 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9966
Blood Brain Barrier+0.9979
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.8631
P-glycoprotein inhibitor IInhibitor0.5435
P-glycoprotein inhibitor IINon-inhibitor0.8724
Renal organic cation transporterInhibitor0.638
CYP450 2C9 substrateNon-substrate0.7698
CYP450 2D6 substrateSubstrate0.9274
CYP450 3A4 substrateSubstrate0.7796
CYP450 1A2 substrateNon-inhibitor0.6494
CYP450 2C9 inhibitorNon-inhibitor0.8866
CYP450 2D6 inhibitorInhibitor0.6978
CYP450 2C19 inhibitorNon-inhibitor0.8256
CYP450 3A4 inhibitorNon-inhibitor0.8899
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.747
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9567
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.8450 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8556
hERG inhibition (predictor II)Non-inhibitor0.8615
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-01ot-3950000000-e80ecb11646b4da6aa92
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL Thermo Scientific) 60V, PositiveLC-MS/MSsplash10-0uxr-0973000000-87d07ddd2ed24b9598d7
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0009000000-d68b67071bf467a42afa
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0009000000-a298cedb776a11677cf7
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0459000000-1a92521b38ba51a7fa81
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0gc1-0940000000-68cae285315cfe9c7d0e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0uxs-0910000000-b0c288c76c616e1a54d3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0159-0390000000-ac30542a576060b3373c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-870de7833257cd342810
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-8ece718ed46e5e439112
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0139000000-7880499a47dbd2f41229
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0973000000-87d07ddd2ed24b9598d7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-015a-0920000000-4f676c9e2b42320493af
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0910000000-e67964930533268605cd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-99b083bf48ae39e3cec6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-efebfbff05a4cb72fe32
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0139000000-be0f9b6eaa028b54ad6c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0973000000-89bc81638a52beefd890
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-015a-0920000000-7eccc8e19d8d88b18128
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0910000000-5809a9ed32210bcfa231
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0159-0390000000-a7469c01c0a4ff4179bf
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0uyi-1952000000-3db61b1a0c8cde5b8c82
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0lea-1940000000-b491506c23f09adaee8c
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0lea-1930000000-48dcc53ac80bf97d1f2d

Taxonomy

Description
This compound belongs to the class of organic compounds known as 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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Morphinans
Sub Class
Not Available
Direct Parent
Morphinans
Alternative Parents
Phenanthrenes and derivatives / Tetralins / Coumarans / Anisoles / Aralkylamines / Alkyl aryl ethers / Piperidines / Trialkylamines / Secondary alcohols / Oxacyclic compounds
show 3 more
Substituents
Morphinan / Phenanthrene / Tetralin / Coumaran / Anisole / Alkyl aryl ether / Aralkylamine / Piperidine / Benzenoid / Secondary alcohol
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid, organic heteropentacyclic compound (CHEBI:16714) / Isoquinoline alkaloids (C06174)

Targets

Details
1. Mu-type opioid receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
References
  1. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed:15509185]
  2. Takahama K, Shirasaki T: Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs. Cough. 2007 Jul 9;3:8. [PubMed:17620111]
  3. Freissmuth M, Beindl W, Kratzel M: Binding and structure-activity-relation of benzo[f]isoquinoline- and norcodeinone-derivatives at mu-opioid receptors in the rat cerebral cortex. Br J Pharmacol. 1993 Dec;110(4):1429-36. [PubMed:8306082]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
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:17139284]
  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:17016423]
  3. Takahama K, Shirasaki T: Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs. Cough. 2007 Jul 9;3:8. [PubMed:17620111]
  4. Mignat C, Wille U, Ziegler A: Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life Sci. 1995;56(10):793-9. [PubMed:7885194]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
References
  1. Ortiz MI, Castro-Olguin J, Pena-Samaniego N, Castaneda-Hernandez G: Probable activation of the opioid receptor-nitric oxide-cyclic GMP-K+ channels pathway by codeine. Pharmacol Biochem Behav. 2005 Dec;82(4):695-703. Epub 2006 Jan 4. [PubMed:16386786]
  2. Mignat C, Wille U, Ziegler A: Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life Sci. 1995;56(10):793-9. [PubMed:7885194]
  3. Loghin F, Popa DS, Socaciu C: Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine treatment. J Cell Mol Med. 2001 Oct-Dec;5(4):409-16. [PubMed:12067475]
  4. Advenier C, Girard V, Naline E, Vilain P, Emonds-Alt X: Antitussive effect of SR 48968, a non-peptide tachykinin NK2 receptor antagonist. Eur J Pharmacol. 1993 Nov 30;250(1):169-71. [PubMed:8119316]
  5. Karlsson JA, Lanner AS, Persson CG: Airway opioid receptors mediate inhibition of cough and reflex bronchoconstriction in guinea pigs. J Pharmacol Exp Ther. 1990 Feb;252(2):863-8. [PubMed:2156065]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF: Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723. doi: 10.2165/11318030-000000000-00000. [PubMed:19817501]
  2. Duquette PH, Peterson FJ, Crankshaw DL, Lindemann NJ, Holtzman JL: Studies of the metabolic N- and O-demethylation of [6-3H]codeine. Drug Metab Dispos. 1983 Sep-Oct;11(5):477-80. [PubMed:6138234]
  3. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Duquette PH, Peterson FJ, Crankshaw DL, Lindemann NJ, Holtzman JL: Studies of the metabolic N- and O-demethylation of [6-3H]codeine. Drug Metab Dispos. 1983 Sep-Oct;11(5):477-80. [PubMed:6138234]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Tzvetkov MV, dos Santos Pereira JN, Meineke I, Saadatmand AR, Stingl JC, Brockmoller J: Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochem Pharmacol. 2013 Sep 1;86(5):666-78. doi: 10.1016/j.bcp.2013.06.019. Epub 2013 Jul 5. [PubMed:23835420]

Drug created on June 13, 2005 07:24 / Updated on September 20, 2018 12:15