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Drug

D0038 | Diclofenac

Molecular Formula C14H11Cl2NO2
Molecular Weight 296.1
Structure
State solid
Clearance * oral cl=622 mL/min [healthy] * renal cl <1 mL/min [healthy]
Volume of distribution * 1.3 L/kg
Route of elimination Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites.
Protein binding More than 99%
Half life 2 hours
Absorption Completely absorbed from the gastrointestinal tract.
Trade names Cataflam, Voltaren
Description phenylacetic acid derivative; non-steroidal anti-inflammatory drug (NSAID); non-selective COX inhibitor; Anti-inflammatory

S

M

D

S01CC01 Diclofenac and antiinfectives


[S01CC] Antiinflammatory agents, non-steroids and antiinfectives in combination


[S01C] ANTIINFLAMMATORY AGENTS AND ANTIINFECTIVES IN COMBINATION


[S01] OPHTHALMOLOGICALS


[S] Sensory organs

S01BC03 Diclofenac


[S01BC] Antiinflammatory agents, non-steroids


[S01B] ANTIINFLAMMATORY AGENTS


[S01] OPHTHALMOLOGICALS


[S] Sensory organs

M02AA15 Diclofenac


[M02AA] Antiinflammatory preparations, non-steroids for topical use


[M02A] TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN


[M02] TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN


[M] Musculoskeletal system

M01AB55 Diclofenac, combinations


[M01AB] Acetic acid derivatives and related substances


[M01A] ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS


[M01] ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS


[M] Musculoskeletal system

M01AB05 Diclofenac


[M01AB] Acetic acid derivatives and related substances


[M01A] ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS


[M01] ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS


[M] Musculoskeletal system

D11AX18 Diclofenac


[D11AX] Other dermatologicals


[D11A] OTHER DERMATOLOGICAL PREPARATIONS


[D11] OTHER DERMATOLOGICAL PREPARATIONS


[D] Dermatological drugs

Toxicity Dose Time Species Model Method Action Positive criterion Reference
TRANSMEMBRANE POTENTIAL 487 24hr rat hepatocytes tetramethylrhodamine ethyl ester (TMRE) decrease AC50 (μM) 40
PERMEABILIZATION 12.5 μmol/L 10 minutes rat liver mitochondria Assessment of MPT increase not mentioned 6
PERMEABILIZATION 25 μmol/L 10 minutes rat liver mitochondria Assessment of MPT increase not mentioned 6
PERMEABILIZATION 50 μmol/L 10 minutes rat liver mitochondria Assessment of MPT increase not mentioned 6
PERMEABILIZATION 100 μmol/L 10 minutes rat liver mitochondria Assessment of MPT increase not mentioned 6
UNCOUPLING increase 39
UNCOUPLING rat heart 197
UNCOUPLING 197
PROTONOPHORIC UNCOUPLING 278
MEMBRANE POTENTIAL 50 μmol/L 3 minutes rat liver mitochondria Assessment of Mitochondrial Membrane Potential; incubated in the presence of Ca2+ decrease p < 0.01 6
MEMBRANE POTENTIAL 50 μmol/L 3 minutes rat liver mitochondria Assessment of Mitochondrial Membrane Potential; incubated in the absence of Ca2+ Negative p < 0.05 6
MEMBRANE POTENTIAL 250 μmol/L 24 hours rat hepatocytes Assessment of Mitochondrial Membrane Potential decrease p < 0.01 6
MEMBRANE POTENTIAL 500 μmol/L 24 hours rat hepatocytes Assessment of Mitochondrial Membrane Potential decrease p < 0.01 6
MEMBRANE POTENTIAL 137.9 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION 9.1 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION 29.8 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. decrease EC20 36
STATE 2 RESPIRATION 56.3 ± 4.9 rat isolated rat liver mitochondria State 2 respiration ( 96-well plate format using a phosphorescent oxygen-sensitive probe MitoXpress) inhibit UC50 (nmol/mg mitochondrial protein) 40
STATE 3 RESPIRATION 100 nmol/mg mitochondrial protein rat isolated rat liver mitochondria State 3 respiration ( 96-well plate format using a phosphorescent oxygen-sensitive probe MitoXpress) Negative IC50 (nmol/mg mitochondrial protein) 40
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex V activity decrease p < 0.01 3
ELECTRON TRANSPORT CHAIN decrease 39
LIPID METABOLISM 122 24hr rat hepatocytes LipidTox, for neutral lipid accumulation, to evaluate lipid content. accumulation AC50 (μM) 40
MITOCHONDRIAL FATTY ACID BETA OXIDATION 47μM 11* mice Lean mice vs Ob/ob mice Measurement of oxygen consumption in the presence of ADP (state 3) and the different substrates was carried out on the Mitologics screening platform EC20 227
ACCUMULATION OF CALCIUM 50 μmol/L 2 minutes rat liver mitochondria Assessment of Mitochondrial Ca2+ Efflux; Energized with succinate decrease not mentioned 6
ATP SYNTHESIS 250 μmol/L 24 hours rat hepatocytes Assay of Cellular ATP contents; Assay of LDH leakage decrease p < 0.01 6
ATP SYNTHESIS 500 μmol/L 24 hours rat hepatocytes Assay of Cellular ATP contents; Assay of LDH leakage decrease p < 0.01 6
NADPH METABOLISM 50 μmol/L 10 minutes rat liver mitochondria Measurement of Mitochondrial NADPH; incubated in the presence of Ca2+ increase p < 0.01 6
NADPH METABOLISM 50 μmol/L 10 minutes rat liver mitochondria Measurement of Mitochondrial NADPH; incubated in the absence of Ca2+ Negative p < 0.05 6
THIOL COMPOUNDS METABOLISM 50 μmol/L 10 minutes rat liver mitochondria Assay of Mitochondrial Protein Thiol; Assay of Mitochondrial GSH; incubated in the presence of Ca2+ decrease p < 0.01 6
THIOL COMPOUNDS METABOLISM 50 μmol/L 10 minutes rat liver mitochondria Assay of Mitochondrial Protein Thiol; Assay of Mitochondrial GSH; incubated in the absence of Ca2+ Negative p < 0.05 6
GLUTATHIONE METABOLISM 167 24hr rat hepatocytes glutathion depletion: cells were incubated with 50 μM monochlorobimane with 6 μg/ml Hoechst 33342 AC50 (μM) 40
SWELLING > 800 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36
ROS PRODUCTION NR rat hepatocytes use CM-H2DCFDA to monitor reactive oxygen species Negative AC50 (μM) 40
CYTOCHROME C RELEASE 197 24hr rat hepatocytes cytochrome c release (anti-cytochrome c antibody ) induce AC50 (μM) 40
ER STRESS-INDUCED 51 24hr rat hepatocytes DNA damage 153 induction (GADD153 antibodies) for ER-stress induced apoptosis induce AC50 (μM) 40

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
NADH:ubiquinone reductase inhibitor 39
NADH:ubiquinone reductase 9.1 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Succinate dehydrogenase 29.8 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. inhibit EC20 36
Quinol--cytochrome-c reductase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Cytochrome c oxidase 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ATP synthase 50 μM bovine heart mitochondria Measurement of complex V activity inhibitor p < 0.01 3
ATP 250 μmol/L 24 hours rat hepatocytes Assay of Cellular ATP contents; Assay of LDH leakage decrease p < 0.01 6
ATP 500 μmol/L 24 hours rat hepatocytes Assay of Cellular ATP contents; Assay of LDH leakage decrease p < 0.01 6
Thiol compounds 50 μmol/L 10 minutes rat liver mitochondria Assay of Mitochondrial Protein Thiol; Assay of Mitochondrial GSH; incubated in the presence of Ca2+ decrease p < 0.01 6
Thiol compounds 50 μmol/L 10 minutes rat liver mitochondria Assay of Mitochondrial Protein Thiol; Assay of Mitochondrial GSH; incubated in the absence of Ca2+ Negative p < 0.05 6
Cytochrome c > 200 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 62 companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


Reported as not meeting GHS hazard criteria by 1 of 62 companies. For more detailed information, please visit ECHA C&L website


Of the 10 notification(s) provided by 61 of 62 companies with hazard statement code(s):


H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]


H311 (90.16%): Toxic in contact with skin [Danger Acute toxicity, dermal]


H315 (88.52%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (88.52%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H335 (88.52%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure


Respiratory tract irritation]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P337+P313, P361, P362, P363, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

Aggregated GHS information provided by 294 companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


Reported as not meeting GHS hazard criteria by 52 of 294 companies. For more detailed information, please visit ECHA C&L website


Of the 11 notification(s) provided by 242 of 294 companies with hazard statement code(s):


H301 (16.12%): Toxic if swallowed [Danger Acute toxicity, oral]


H302 (83.88%): Harmful if swallowed [Warning Acute toxicity, oral]


H361 (73.55%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H372 (68.18%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


H411 (82.64%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P264, P270, P273, P281, P301+P310, P301+P312, P308+P313, P314, P321, P330, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
man TDLo intramuscular 1070ug/kg (1.07mg/kg) skin and appendages (skin): "dermatitis, other: after systemic exposure" Annals of Internal Medicine. Vol. 117, Pg. 1058, 1992.
mouse LD50 intraperitoneal 345mg/kg (345mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 43, Pg. 44, 1993.
man TDLo oral 29mg/kg (29mg/kg) blood: "changes in serum composition (e.g., tp, bilirubin, cholesterol)" Journal of Toxicology, Clinical Toxicology. Vol. 33, Pg. 173, 1995.
mouse LD50 oral 170mg/kg (170mg/kg) Pharmazie. Vol. 37, Pg. 148, 1982.
rat LD50 oral 62500ug/kg (62.5mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 30, Pg. 1398, 1980.

  • Actinic keratosis

  • Ankylosing spondylitis

  • Arthritis

  • Aura

  • Biliary colic

  • Body temperature increased

  • Cataract

  • Chronic hepatitis

  • Cluster headache

  • Contusion

  • Convulsion

  • Ear infection

  • Effusion

  • Foetor hepaticus

  • Gastrointestinal disorder

  • Gout

  • Hepatic cirrhosis

  • Hepatic function abnormal

  • Hepatocellular injury

  • Hypotension

  • Infection

  • Inflammation

  • Injury

  • Juvenile idiopathic arthritis

  • Ligament sprain

  • Pharyngotonsillitis

  • Photophobia

  • Polyuria

  • Post-traumatic pain

  • Procedural pain

  • Pulmonary function test decreased

  • Renal colic

  • Renal impairment

  • Respiratory depression

  • Rheumatic disorder

  • Rheumatoid arthritis

  • Salpingo-oophoritis

  • Seborrhoeic keratosis

  • Spinal osteoarthritis

  • Spondylitis

  • Swelling

  • Vomiting

  • Wound

  • Abdominal discomfort (0.02)

  • Urticaria (0.002)

  • Abdominal pain

  • Abdominal pain upper

  • Acne

  • Alanine aminotransferase increased

  • Alopecia

  • Anxiety

  • Application site dryness

  • Application site erythema

  • Application site induration

  • Application site irritation

  • Application site papules

  • Application site paraesthesia

  • Application site pruritus

  • Application site rash

  • Application site reaction

  • Application site vesicles

  • Arthralgia

  • Arthropathy

  • Aspartate aminotransferase increased

  • Asthenia

  • Asthma

  • Back pain

  • Blood creatine phosphokinase increased

  • Blood creatinine increased

  • Breath odour

  • Chest pain

  • Chills

  • Conjunctivitis

  • Constipation

  • Contusion

  • Dermatitis

  • Dermatitis bullous

  • Dermatitis contact

  • Diarrhoea

  • Dizziness

  • Dry skin

  • Dysgeusia

  • Dyspepsia

  • Dyspnoea

  • Ecchymosis

  • Eye pain

  • Flatulence

  • Gastrointestinal disorder

  • Gastrointestinal pain

  • Haematuria

  • Headache

  • Herpes simplex

  • Hyperaesthesia

  • Hypercholesterolaemia

  • Hyperglycaemia

  • Hypersensitivity

  • Hypertension

  • Hypokinesia

  • Induration

  • Infection

  • Influenza

  • Injury

  • Malnutrition

  • Migraine

  • Musculoskeletal discomfort

  • Myalgia

  • Nausea

  • Neck pain

  • Nervous system disorder

  • Oedema

  • Osteoarthritis

  • Pain

  • Pain in extremity

  • Paraesthesia

  • Pharyngitis

  • Phlebitis

  • Photosensitivity reaction

  • Pneumonia

  • Pruritus

  • Rash

  • Rash maculo-papular

  • Rash pustular

  • Sinus congestion

  • Sinusitis

  • Skin cancer

  • Skin exfoliation

  • Skin mass

  • Skin ulcer

  • Somnolence

  • Urinary tract infection

  • Vomiting

    • (2-((2,6-Dichlorophenyl)amino-phenyl)acetic acid (HD) 056D694 144O8QL0L1
    15307-86-5 2-((2,6-Dichlorophenyl)amino)benzeneacetic acid 2-(2,6-Dichloroanilino)phenylacetic Acid
    2-(2-((2,6-Dichlorophenyl)amino)phenyl)acetic acid 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid 2-[(2,6-Dichlorophenyl)amino]benzeneacetic acid
    2-[(2,6-dichlorophenyl)-amino]-benzeneacetic acid 2-[(2,6-dichlorophenyl)-amino]-phenyl-acetic acid 2-[(2,6-dichlorophenyl)amino]-benzeneacetic acid
    2-[(2,6-dichlorophenyl)amino]-phenyl-acetic acid 2-[(2,6-dichlorophenyl)amino]phenylacetic acid 2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID
    2-[2-(2,6-Dichlorophenyl)aminophenyl]ethanoic acid 2-[2-(2,6-dichloroanilino)phenyl]acetic acid 2-[2-(2,6-dichloroanilino)phenyl]acetic acid.
    2-[2-(2,6-dichlorophenyl)aminophenyl]ethanoic acid 2-[2-(2,6-dichlorophenylamino)-phenyl]-acetic acid 2-[2-(2,6-dichlorophenylamino)phenyl]-acetic acid
    2-[2-[(2,6-Dichlorophenyl)amino]phenyl]acetic Acid (Diclofenac) 2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
    2b17 AB01275502-01 AB01275502_02
    AB1009343 AC-27673 ACETIC ACID, (o-(2,6-DICHLOROANILINO)PHENYL)-
    ACMC-209d8r AK-75694 AKOS001579542
    ANW-21433 Arthrotec BCP09087
    BCP13860 BDBM13066 BIDD:GT0380
    BPBio1_000516 BRD-K08252256-236-05-6 BRD-K08252256-236-17-1
    BRN 2146636 BSPBio_000468 BSPBio_002169
    Benzeneacetic acid, 2-((2,6-dichlorophenyl)amino)- Benzeneacetic acid, 2-((2,6-dichlorophenyl)amino)- (9CI) Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-
    C01690 CHEBI:47381 CHEMBL139
    CS-2862 CTK8B0851 D07816
    D3748 DB00586 DCOPUUMXTXDBNB-UHFFFAOYSA-N
    DIF DTXSID6022923 Dichlofenal
    Diclofenac (USAN/INN) Diclofenac [INN:BAN] Diclofenac [USAN:INN:BAN]
    Diclofenac acid Diclofenac resinate Diclofenaco
    Diclofenaco [INN-Spanish] Diclofenacum Diclofenacum [INN-Latin]
    Diclofenamic acid Diclonate P Diclophenac
    Dicrofenac DivK1c_000272 DivK1c_000402
    EBD50236 EC 239-348-5 EINECS 239-348-5
    Epitope ID:116873 F0722-0745 FT-0624731
    GP-45,840 GP-45840 GTPL2714
    HMS2090C10 HMS501E04 HSDB 7234
    HY-15036 IDI1_000272 IDI1_000402
    ISV-205 KBio1_000272 KBio1_000402
    KBio2_001410 KBio2_002306 KBio2_003978
    KBio2_004874 KBio2_006546 KBio2_007442
    KBio3_001389 KBio3_002786 KBioGR_001051
    KBioGR_002306 KBioSS_001410 KBioSS_002308
    KS-000001OB KS-1258 LS-11575
    Lopac0_000441 M-7482 MCULE-1824024270
    MLS006011795 NCGC00021125-01 NCGC00021125-02
    NINDS_000272 NINDS_000402 Novapirina
    Olfen Oprea1_011155 Pennsaid
    Prestwick0_000594 Prestwick1_000594 Prestwick2_000594
    Prestwick3_000594 ProSorb-D Q244408
    SBI-0051341.P003 SC-16284 SCHEMBL2799
    SMR001550371 SPBio_001081 SPBio_002687
    SR-01000003041-3 SR-38 ST51039044
    STK984493 Solaraze Solaraze (TN)
    Spectrum2_000991 Spectrum3_000385 Spectrum4_000506
    Spectrum5_000867 Spectrum_000930 TC-110178
    UNII-144O8QL0L1 UNM000001216103 Voltaren
    Voltaren-XR Voltarol Z57664869
    ZINC1281 Zorovolex Zorvolex
    Zorvolex (TN) [2-(2,6-Dichloroanilino)phenyl]-acetic acid [2-(2,6-Dichloroanilino)phenyl]acetic acid
    [2-(2,6-Dichloroanilino)phenyl]acetic acid # [2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid [o-(2,6-dichloro-anilino)-phenyl]-acetic acid
    cMAP_000014 dichlofenac diclofenac
    o-(2,6-dichloroanilino)phenylacetic acid {2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid

    DrugBank Name Diclofenac
    DrugBank DB00586
    CAS Number 119623-66-4, 128402-48-2, 15307-86-5, 15362-40-0, 23049-93-6, 78213-16-8, 79183-19-0
    PubChem Compound 3033
    KEGG Compound ID C01690
    KEGG Drug D07816
    PubChem.Substance 46504644
    ChEBI 47381
    PharmGKB PA449293
    ChemSpider 2925
    BindingDB 13066.0
    TTD DAP000620
    Wikipedia Diclofenac
    HET DIF
    DPD 2013|1205|20061

    1. Dykens et al. (2007)
    2. Krause et al. (2003)
    3. Moreno-Sanchez et al. (1999)
    4. Vuda et al. (2016)
    5. Chan et al. (2005)