rofecoxib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
selective cyclo-oxygenase inhibitors 2397 162011-90-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • rofecoxib
  • vioxx
  • ceeoxx
a sulfonylphenyl furanone; withdrawn out of concern for TOXICITY
  • Molecular weight: 314.36
  • Formula: C17H14O4S
  • CLOGP: 1.80
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 0
  • TPSA: 60.44
  • ALOGS: -4.47
  • ROTB: 3
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
25 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.10 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 2.65 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 93 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.30 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.13 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 7.50 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.536 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.652 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 69.343 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 10.209 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 19.490 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 35.940 % High 1
herg hERG pIC50 4.651 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 8.790 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.613 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 11.390 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,GRK2,ITK,MAPK10,MAPK7,PDK1,PDK2,PDK4,PIK3CB,PIK3CD,PIK3CG,PRKDC,STK33,TEK,TTK 25
kinase-selectivity-class AXL,GRK2,PDK4 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.959 High 1
mh-clint Mouse hepatocyte intrinsic clearance 17.338 High 1
mppb Mouse plasma protein binding (% unbound) 13.300 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 4.036 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 28.570 % High 1
rh-clint Rat hepatocyte intrinsic clearance 25.527 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 81.430 % High 1
rppb Rat plasma protein binding (% unbound) 13.020 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 53.088 uM High 1

Approvals:

DateAgencyCompanyOrphan
May 20, 1999 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug hypersensitivity 543.07 38.99 294 3391 463315 90161447
Oesophageal spasm 181.84 38.99 39 3646 3322 90621440
Oesophageal pain 171.61 38.99 39 3646 4335 90620427
Stress 169.37 38.99 77 3608 81318 90543444
Lymphoedema 127.31 38.99 39 3646 13714 90611048
Sleep apnoea syndrome 102.30 38.99 41 3644 31706 90593056
Tinnitus 96.59 38.99 43 3642 43059 90581703
Anaphylactic reaction 85.98 38.99 50 3635 87474 90537288
Drug ineffective 76.00 38.99 170 3515 1384128 89240634
Cystitis 75.99 38.99 42 3643 66676 90558086
Spinal cord infection 72.07 38.99 14 3671 725 90624037
Hallucination 70.97 38.99 40 3645 65919 90558843
Mucosal erosion 69.91 38.99 16 3669 1829 90622933
Agitation 67.64 38.99 39 3646 67059 90557703
Drug intolerance 66.39 38.99 86 3599 447505 90177257
Fluid retention 62.72 38.99 41 3644 88050 90536712
Nasopharyngitis 61.56 38.99 79 3606 407025 90217737
Vision blurred 61.17 38.99 44 3641 110249 90514513
Bronchitis 58.62 38.99 49 3636 152878 90471884
Myocardial infarction 55.86 38.99 41 3644 105931 90518831
Genital erosion 52.78 38.99 10 3675 453 90624309
Hyperhidrosis 48.79 38.99 42 3643 136263 90488499
Hepatic fibrosis 47.97 38.99 14 3671 4161 90620601
Impaired work ability 45.57 38.99 20 3665 19306 90605456
Feeling abnormal 45.15 38.99 44 3641 167191 90457571

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Acne cystic 261.37 53.00 38 1036 544 42619717
Drug intolerance 103.74 53.00 47 1027 80377 42539884
Abdominal discomfort 103.50 53.00 46 1028 75209 42545052
Ankylosing spondylitis 79.59 53.00 21 1053 7035 42613226
Insomnia 78.24 53.00 44 1030 118209 42502052
Sacroiliitis 70.73 53.00 15 1059 1967 42618294
Drug ineffective 70.61 53.00 82 992 630115 41990146
Chest expansion decreased 53.14 53.00 8 1066 145 42620116

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug hypersensitivity 425.82 45.88 233 3452 453857 110131757
Oesophageal spasm 203.65 45.88 42 3643 3624 110581990
Oesophageal pain 189.62 45.88 42 3643 5083 110580531
Stress 161.93 45.88 76 3609 105272 110480342
Lymphoedema 145.04 45.88 42 3643 14887 110570727
Sleep apnoea syndrome 114.48 45.88 45 3640 40402 110545212
Tinnitus 90.80 45.88 43 3642 60497 110525117
Drug ineffective 89.69 45.88 171 3514 1520369 109065245
Nasopharyngitis 87.54 45.88 85 3600 394276 110191338
Drug intolerance 87.22 45.88 86 3599 406426 110179188
Cystitis 84.28 45.88 42 3643 65994 110519620
Anaphylactic reaction 82.84 45.88 50 3635 114250 110471364
Fluid retention 72.86 45.88 43 3642 94264 110491350
Hallucination 72.52 45.88 44 3641 101388 110484226
Bronchitis 68.36 45.88 50 3635 156982 110428632
Mucosal erosion 66.30 45.88 16 3669 2808 110582806
Agitation 65.68 45.88 43 3642 113008 110472606
Vision blurred 62.85 45.88 44 3641 128978 110456636
Myocardial infarction 61.52 45.88 51 3634 192032 110393582
Ankylosing spondylitis 57.24 45.88 21 3664 15591 110570023
Hyperhidrosis 54.36 45.88 47 3638 187251 110398363
Feeling abnormal 53.77 45.88 46 3639 180665 110404949
Migraine 51.69 45.88 44 3641 171608 110414006
Genital erosion 49.18 45.88 10 3675 801 110584813
Sacroiliitis 48.29 45.88 14 3671 4964 110580650
Chest expansion decreased 48.27 45.88 8 3677 204 110585410
Fibromyalgia 47.79 45.88 42 3643 170867 110414747
Anxiety 47.65 45.88 58 3627 345020 110240594
Depression 46.54 45.88 55 3630 317280 110268334
Bone erosion 46.21 45.88 25 3660 46346 110539268

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC M01AH02 MUSCULO-SKELETAL SYSTEM
ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
Coxibs
MeSH PA D000700 Analgesics
MeSH PA D000893 Anti-Inflammatory Agents
MeSH PA D000894 Anti-Inflammatory Agents, Non-Steroidal
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D016861 Cyclooxygenase Inhibitors
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018501 Antirheumatic Agents
MeSH PA D018689 Sensory System Agents
MeSH PA D018712 Analgesics, Non-Narcotic
MeSH PA D052246 Cyclooxygenase 2 Inhibitors
CHEBI has role CHEBI:35475 non-steroidal anti-inflammatory drug
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50629 cyclooxygenase 2 inhibitor
CHEBI has role CHEBI:67079 anti-inflammatory agent

Related Drugs by ATC class:

M01AH Coxibs 6 drugs
celecoxibetoricoxiblumiracoxibparecoxibpolmacoxibvaldecoxib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Pain indication 22253000
Migraine indication 37796009 DOID:6364
Rheumatoid arthritis indication 69896004 DOID:7148
Dysmenorrhea indication 266599000
Osteoarthritis indication 396275006
Juvenile rheumatoid arthritis indication 410795001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Prostaglandin G/H synthase 2 Enzyme INHIBITOR IC50 6.51 WOMBAT-PK CHEMBL
Prostaglandin G/H synthase 1 Enzyme IC50 5.77 CHEMBL
Prostaglandin E2 receptor EP2 subtype GPCR Ki 7.47 PDSP
Cytochrome c oxidase subunit 2 Enzyme IC50 5.52 CHEMBL
Prostaglandin G/H synthase 2 Enzyme IC50 7.92 CHEMBL
Prostaglandin G/H synthase 1 Enzyme IC50 4.63 CHEMBL
Prostaglandin G/H synthase 2 Enzyme IC50 6.37 CHEMBL
Prostaglandin G/H synthase 2 Enzyme IC50 6.12 CHEMBL
Prostaglandin G/H synthase 1 Enzyme IC50 4.94 CHEMBL
Prostaglandin G/H synthase 2 Enzyme IC50 6.52 CHEMBL

External reference:

IDSource
4021160 VUID
N0000148611 NUI
D00568 KEGG_DRUG
4021160 VANDF
C0762662 UMLSCUI
CHEBI:8887 CHEBI
RCX PDB_CHEM_ID
CHEMBL122 ChEMBL_ID
DB00533 DRUGBANK_ID
C116926 MESH_SUPPLEMENTAL_RECORD_UI
5090 PUBCHEM_CID
2893 IUPHAR_LIGAND_ID
7768 INN_ID
0QTW8Z7MCR UNII
232158 RXNORM
30883 MMSL
8220 MMSL
d04433 MMSL
007787 NDDF
116095002 SNOMEDCT_US
387008005 SNOMEDCT_US
0QTW8Z7MCR INXIGHT DRUGS

Pharmaceutical products:

None