Identification

Name
Parecoxib
Accession Number
DB08439
Type
Small Molecule
Groups
Approved
Description

Parecoxib is a water-soluble and injectable prodrug of valdecoxib. It is marketed as Dynastat in the European Union. Parecoxib is a COX2 selective inhibitor in the same category as celecoxib (Celebrex) and rofecoxib (Vioxx). As it is injectable, it can be used perioperatively when patients are unable to take oral medications. It is approved through much of Europe for short term perioperative pain control much in the same way ketorolac (Toradol) is used in the United States. In 2005, the U.S. Food and Drug Administration (FDA) issued a letter of non-approval for parecoxib in the United States.

Structure
Thumb
Synonyms
  • parecoxib
External IDs
SC 69124 / SC-69124
Product Ingredients
IngredientUNIICASInChI Key
Parecoxib sodiumEB87433V6F198470-85-8HQPVVKXJNZEAFW-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DynastatInjection, powder, for solution40 mgIntramuscular; IntravenousPfizer2002-03-22Not applicableEu
DynastatInjection, powder, for solution40 mgIntramuscular; IntravenousPfizer2002-03-22Not applicableEu
DynastatInjection, powder, for solution40 mgIntramuscular; IntravenousPfizer2002-03-22Not applicableEu
DynastatInjection, powder, for solution40 mgIntramuscular; IntravenousPfizer2002-03-22Not applicableEu
International/Other Brands
Dynastat
Categories
UNII
9TUW81Y3CE
CAS number
198470-84-7
Weight
Average: 370.422
Monoisotopic: 370.098727764
Chemical Formula
C19H18N2O4S
InChI Key
TZRHLKRLEZJVIJ-UHFFFAOYSA-N
InChI
InChI=1S/C19H18N2O4S/c1-3-17(22)21-26(23,24)16-11-9-14(10-12-16)18-13(2)25-20-19(18)15-7-5-4-6-8-15/h4-12H,3H2,1-2H3,(H,21,22)
IUPAC Name
N-[4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)benzenesulfonyl]propanamide
SMILES
CCC(=O)NS(=O)(=O)C1=CC=C(C=C1)C1=C(C)ON=C1C1=CC=CC=C1

Pharmacology

Indication

Used for short term perioperative pain control.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
ULactotransferrinNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

98%

Metabolism

Hepatic. Metabolized primarily via CYP3A4 and 2C9 to valdecoxib and propionic acid.

Route of elimination
Not Available
Half life

22 minutes (parecoxib); 8 hours (valdecoxib)

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when Parecoxib is combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Parecoxib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Parecoxib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Parecoxib.
5-androstenedioneThe metabolism of Parecoxib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Parecoxib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Parecoxib.
AbacavirParecoxib may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Parecoxib is combined with Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Parecoxib.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D02709
PubChem Compound
119828
PubChem Substance
99444910
ChemSpider
106990
ChEBI
73038
ChEMBL
CHEMBL1206690
PharmGKB
PA166049193
HET
PXB
Wikipedia
Parecoxib
ATC Codes
M01AH04 — Parecoxib
PDB Entries
2zmb

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionPost-Operative Pain / Shoulder Pain1
2, 3CompletedNot AvailablePostoperative analgesia for TKA Parecoxib/CFB1
3CompletedTreatmentPostoperative pain1
3Not Yet RecruitingTreatmentParecoxib / Rib Fractures1
3RecruitingTreatmentLiver Cancer / Postoperative pain1
3TerminatedTreatmentColic1
3TerminatedTreatmentPain NOS1
4CompletedBasic ScienceSecondary Hyperalgesia1
4CompletedPreventionPostoperative Pain Management, Pain Threshold, Shoulder Pain, Laparoscopies1
4CompletedPreventionPostoperative pain1
4CompletedSupportive CarePostoperative pain1
4CompletedTreatmentAnaesthesia1
4CompletedTreatmentInflammatory Reaction / Pain NOS1
4CompletedTreatmentPain NOS1
4CompletedTreatmentPost-Operative Pain1
4CompletedTreatmentPostoperative Shivering1
4CompletedTreatmentPostoperative pain2
4CompletedTreatmentRupture of Anterior Cruciate Ligament1
4TerminatedTreatmentPost Surgical Pain1
4TerminatedTreatmentPostoperative pain1
4Unknown StatusSupportive CareGastrointestinal Cancers1
4Unknown StatusTreatmentEmergence Delirium / Postoperative pain1
4Unknown StatusTreatmentHepatic Hemangioma Located in the Right Liver / Laparotomy Surgery1
4WithdrawnTreatmentPostoperative pain1
Not AvailableCompletedNot AvailableHepatocellular,Carcinoma1
Not AvailableCompletedBasic SciencePlatelet Aggregation1
Not AvailableCompletedTreatmentAnti-Inflammatory Agents, Non-Steroidal / Laparoscopy / Postoperative pain1
Not AvailableCompletedTreatmentBenign Female Reproductive System Neoplasm1
Not AvailableCompletedTreatmentPostoperative pain1
Not AvailableNo Longer AvailableNot AvailableComplex Regional Pain Syndrome Type II1
Not AvailableNot Yet RecruitingTreatmentAcute Renal Colic / Ureteric Stone1
Not AvailableUnknown StatusTreatmentPostoperative pain1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntramuscular; Intravenous40 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0162 mg/mLALOGPS
logP3.42ALOGPS
logP3.51ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)4.24ChemAxon
pKa (Strongest Basic)0.42ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area89.27 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity98.9 m3·mol-1ChemAxon
Polarizability38 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8694
Caco-2 permeable-0.644
P-glycoprotein substrateNon-substrate0.8144
P-glycoprotein inhibitor INon-inhibitor0.7995
P-glycoprotein inhibitor IINon-inhibitor0.8537
Renal organic cation transporterNon-inhibitor0.8889
CYP450 2C9 substrateNon-substrate0.702
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.6159
CYP450 1A2 substrateNon-inhibitor0.8459
CYP450 2C9 inhibitorInhibitor0.801
CYP450 2D6 inhibitorNon-inhibitor0.8356
CYP450 2C19 inhibitorInhibitor0.6608
CYP450 3A4 inhibitorNon-inhibitor0.5165
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8722
Ames testNon AMES toxic0.7504
CarcinogenicityCarcinogens 0.5086
BiodegradationNot ready biodegradable0.9899
Rat acute toxicity2.2665 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9874
hERG inhibition (predictor II)Non-inhibitor0.9083
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 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

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / Sulfonyls / Organosulfonic acids and derivatives / Isoxazoles / Heteroaromatic compounds / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds
show 2 more
Substituents
Benzenesulfonamide / Benzenesulfonyl group / Azole / Isoxazole / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Heteroaromatic compound / Sulfonyl / Oxacycle / Organoheterocyclic compound
show 10 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfonamide, isoxazoles (CHEBI:73038)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Talley JJ, Bertenshaw SR, Brown DL, Carter JS, Graneto MJ, Kellogg MS, Koboldt CM, Yuan J, Zhang YY, Seibert K: N-[[(5-methyl-3-phenylisoxazol-4-yl)-phenyl]sulfonyl]propanamide, sodium salt, parecoxib sodium: A potent and selective inhibitor of COX-2 for parenteral administration. J Med Chem. 2000 May 4;43(9):1661-3. [PubMed:10794682]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase activity
Specific Function
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.Lactotransferrin is a major iron-binding and multifu...
Gene Name
LTF
Uniprot ID
P02788
Uniprot Name
Lactotransferrin
Molecular Weight
78181.225 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

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. Ibrahim AE, Feldman J, Karim A, Kharasch ED: Simultaneous assessment of drug interactions with low- and high-extraction opioids: application to parecoxib effects on the pharmacokinetics and pharmacodynamics of fentanyl and alfentanil. Anesthesiology. 2003 Apr;98(4):853-61. [PubMed:12657846]
  2. DrugBank Entry Valdecoxib (is a prodrug of Valdecoxib) [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. DrugBank Entry Valdecoxib (is a prodrug of Valdecoxib) [Link]
  2. Parecoxib EMA Label [File]

Drug created on September 15, 2010 15:31 / Updated on November 02, 2018 09:09