VALDECOXIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H14N2O3S
Molecular Weight	314.359
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC1=C(C(=NO1)C2=CC=CC=C2)C3=CC=C(C=C3)S(N)(=O)=O

InChI

InChIKey=LNPDTQAFDNKSHK-UHFFFAOYSA-N

InChI=1S/C16H14N2O3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3,(H2,17,19,20)

HIDE SMILES / InChI

Molecular Formula	C16H14N2O3S
Molecular Weight	314.359
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib was manufactured and marketed under the brand name Bextra. Bextra was indicated for relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis. For the treatment of primary dysmenorrhea. But in 2005 FDA requested that Pfizer withdraw Bextra from the American market, because the Agency had concluded that the overall risk versus benefit profile of Bextra was unfavorable. That conclusion was based on the potential increased risk for serious cardiovascular (CV) adverse events, an increased risk of serious skin reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme) compared to other NSAIDs, and the fact that Bextra had not been shown to offer any unique advantages over the other available NSAIDs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-2 196	Inhibitor 8,297		0.005 µM [IC50]
Cyclooxygenase-2 196	Inhibitor 8,297		5.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pain, postoperative 9	Palliative	Approved 8,429	Dynastat
Osteoarthritis 157	Palliative	Withdrawn	BEXTRA
Rheumatoid arthritis 316	Palliative	Withdrawn	BEXTRA
Primary dysmenorrhea 16	Primary	Withdrawn	BEXTRA

C_max

Value	Dose	Analyte	Population
39.3 ng/mL	1 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
16.8 ng/mL	1 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
57.9 ng/mL	2 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
26.4 ng/mL	2 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
276 ng/mL	5 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
66.6 ng/mL	5 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
437 ng/mL	10 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
130 ng/mL	10 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
1013 ng/mL	20 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
263 ng/mL	20 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
1681 ng/mL	40 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
498 ng/mL	40 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
146 ng/mL	10 mg single, oral	VALDECOXIB plasma	Homo sapiens
284 ng/mL	20 mg single, oral	VALDECOXIB plasma	Homo sapiens
568 ng/mL	40 mg single, oral	VALDECOXIB plasma	Homo sapiens
1385 ng/mL	20 mg single, oral	VALDECOXIB serum	Homo sapiens
161.1 ng/mL	10 mg 1 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
16 ng/mL	5 mg single, oral	VALDECOXIB plasma	Homo sapiens
12 ng/mL	10 mg single, oral	VALDECOXIB plasma	Homo sapiens
14 ng/mL	20 mg single, oral	VALDECOXIB plasma	Homo sapiens
1 ng/mL	5 mg single, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
0.8 ng/mL	10 mg single, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
1 ng/mL	20 mg single, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
26 ng/mL	5 mg 2 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
24 ng/mL	10 mg 2 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
26 ng/mL	20 mg 2 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
2 ng/mL	5 mg 2 times / day steady-state, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
2 ng/mL	10 mg 2 times / day steady-state, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
2 ng/mL	20 mg 2 times / day steady-state, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
37.3 ng × h/mL	1 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
127 ng × h/mL	1 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
41.9 ng × h/mL	2 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
258 ng × h/mL	2 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
130 ng × h/mL	5 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
563 ng × h/mL	5 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
275 ng × h/mL	10 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
1133 ng × h/mL	10 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
579 ng × h/mL	20 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
2782 ng × h/mL	20 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
1167 ng × h/mL	40 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
5215 ng × h/mL	40 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
1787 ng × h/mL	10 mg single, oral	VALDECOXIB plasma	Homo sapiens
3450 ng × h/mL	20 mg single, oral	VALDECOXIB plasma	Homo sapiens
6957 ng × h/mL	40 mg single, oral	VALDECOXIB plasma	Homo sapiens
9062 ng × h/mL	20 mg single, oral	VALDECOXIB serum	Homo sapiens
1479 ng × h/mL	10 mg 1 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
198 ng × h/mL	5 mg single, oral	VALDECOXIB plasma	Homo sapiens
167 ng × h/mL	10 mg single, oral	VALDECOXIB plasma	Homo sapiens
175 ng × h/mL	20 mg single, oral	VALDECOXIB plasma	Homo sapiens
18 ng × h/mL	5 mg single, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
15 ng × h/mL	10 mg single, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
19 ng × h/mL	20 mg single, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
332 ng × h/mL	5 mg 2 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
341 ng × h/mL	10 mg 2 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
371 ng × h/mL	20 mg 2 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens
31 ng × h/mL	5 mg 2 times / day steady-state, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
33 ng × h/mL	10 mg 2 times / day steady-state, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens
36 ng × h/mL	20 mg 2 times / day steady-state, oral	1-HYDROXYVALDECOXIB plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
0.36 h	1 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
6.83 h	1 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
0.43 h	2 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
6.28 h	2 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
0.25 h	5 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
5.67 h	5 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
0.41 h	10 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
5.44 h	10 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
0.48 h	20 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
9.94 h	20 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
0.87 h	40 mg single, intramuscular	PARECOXIB plasma	Homo sapiens
7.35 h	40 mg single, intramuscular	VALDECOXIB plasma	Homo sapiens
8.31 h	10 mg single, oral	VALDECOXIB plasma	Homo sapiens
8.53 h	20 mg single, oral	VALDECOXIB plasma	Homo sapiens
8.84 h	40 mg single, oral	VALDECOXIB plasma	Homo sapiens
3.7 h	20 mg single, oral	VALDECOXIB serum	Homo sapiens
8.11 h	10 mg 1 times / day steady-state, oral	VALDECOXIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
2%			PARECOXIB plasma	Homo sapiens
2%	10 mg 1 times / day steady-state, oral		VALDECOXIB plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
80 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 18-92	Other AEs: Gastrointestinal ulcer haemorrhage...
40 mg 1 times / day multiple, oral Recommended	unhealthy, 32.3 ±10.9	Disc. AE: Allergic rash, Dizziness... Other AEs: Dyspepsia, Gastritis...
40 mg 2 times / day multiple, oral Highest studied dose	unhealthy	Disc. AE: Hypertension, Peripheral edema...
10 mg 1 times / day multiple, oral Recommended	unhealthy	Disc. AE: Gastrointestinal perforation, Gastrointestinal ulcer... Other AEs: Exfoliative dermatitis...
10 mg 1 times / day multiple, oral Recommended	unhealthy	Disc. AE: Toxic epidermal necrolysis, Stevens-Johnson syndrome...

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AEs

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AE	Significance	Dose	Population
Gastrointestinal ulcer haemorrhage	significant, 0.48%	80 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 18-92
Dyspepsia	2%	40 mg 1 times / day multiple, oral Recommended	unhealthy, 32.3 ±10.9
Gastritis	5.9%	40 mg 1 times / day multiple, oral Recommended	unhealthy, 32.3 ±10.9
Allergic rash	grade 2, 1% Disc. AE	40 mg 1 times / day multiple, oral Recommended	unhealthy, 32.3 ±10.9
Dizziness	grade 2, 1% Disc. AE	40 mg 1 times / day multiple, oral Recommended	unhealthy, 32.3 ±10.9

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587	substrate 1,037 inhibitor 1,767	substrate 1,217 inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1,478 CYP1A2 1,524 CYP2E1 882 OAT1 599 OAT3 642	CYP2C19 991 CYP1A2 1,054 UGT 192

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 1,692	inhibitor 3,277	no
CYP2D6 1,891	inhibitor 3,277	no
CYP2E1 970	inhibitor 3,277	no
CYP3A4 1,925	inhibitor 3,277	no
OAT1 603	inhibitor 3,277	no

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP2C19 991	substrate 3,367	major
CYP3A4 1,737	substrate 3,367	major	yes (co-administration study)
CYP1A2 1,054	substrate 3,367	minor
CYP2C9 1,037	substrate 3,367	yes
CYP2D6 1,217	substrate 3,367	yes

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63634	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63634
ChemicalBook	CB4754453	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4754453
eMolecules	877479	https://www.emolecules.com/cgi-bin/more?vid=877479
MolPort	MolPort-000-883-874	https://www.molport.com/shop/molecule-link/MolPort-000-883-874
Selleck Chemicals	valdecoxib	http://www.selleckchem.com/products/valdecoxib.html

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PubMed

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Title	Date	PubMed
Parecoxib (parecoxib sodium).	2001	11465874
A double-blind, randomized comparison of intramuscularly and intravenously administered parecoxib sodium versus ketorolac and placebo in a post-oral surgery pain model.	2001 Jul	11519767
The injectable cyclooxygenase-2-specific inhibitor parecoxib sodium has analgesic efficacy when administered preoperatively.	2001 Sep	11524347
Concluding remarks. C0X-2-selective inhibition: a new advance in pain management.	2002	12596801
The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity.	2002	12564662

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Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day.

Route of Administration: Parenteral

In Vitro Use Guide

100 uM parecoxib inhibited rat osteoclast differentiation by 94%

Substance Class	Chemical
Record UNII	2919279Q3W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VALDECOXIB

Official Name

English

SC-65872

Code

English

VALDYN

Brand Name

English

VALDECOXIB [MART.]

Common Name

English

VALDECOXIB [VANDF]

Common Name

English

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Classification Tree

Code System

Code

RHEUMATIC DISEASES

EMA ASSESSMENT REPORTS

VALDYN (WITHDRAWN: ARTHRITIS, RHEUMATOID)

Coxibs

WHO-ATC

M01AH03

PELVIC PAIN

EMA ASSESSMENT REPORTS

BEXTRA (WITHDRAWN: DYSMENORRHEA)

PELVIC PAIN

EMA ASSESSMENT REPORTS

VALDYN (WITHDRAWN: DYSMENORRHEA)

RHEUMATIC DISEASES

EMA ASSESSMENT REPORTS

BEXTRA (WITHDRAWN: OSTEOARTHRITIS)

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Code System

Code

Type

Description

DRUG BANK

DB00580

PRIMARY

HSDB

7302

PRIMARY

MERCK INDEX

m11356

PRIMARY

Merck Index

DRUG CENTRAL

2799

PRIMARY

INN

7815

PRIMARY

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Related Record

Type

Details


					2919279Q3W

VALDECOXIB

EXCRETED UNCHANGED

Interaction Type:

AMOUNT EXCRETED

Qualification:

FECAL; URINE

Amount:

5 % (average)
of the dose


					D8T754TT2I

COX-2

TARGET -> INHIBITOR

Amount:


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Comments:

Plasma protein binding for valdecoxib is about 98% over the concentration range (21-2384 ng/mL).

Interaction Type:

BINDING

Amount:

98 % (average)


					L9DP834D1P

CYTOCHROME P450 2C9

METABOLIC ENZYME -> SUBSTRATE

Amount:


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR

Amount:

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Related Record

Type

Details


					T5Q8Y8772I

1-HYDROXYVALDECOXIB

METABOLITE ACTIVE -> PARENT

Interaction Type:

MINOR

Qualification:

URINE

Amount:

0.3 % (average)
of dose


					8T639S0K61

1-DEOXY-1-(((4-(5-METHYL-3-PHENYL-4-ISOXAZOLYL)PHENYL)SULFONYL)AMINO)-.BETA.-D-GLUCOPYRANURONIC ACID

METABOLITE -> PARENT

Interaction Type:

MAJOR

Qualification:

URINE

Amount:

19.5 % (average)


					6K4X6RVD3Z

.BETA.-D-GLUCOPYRANOSIDURONIC ACID, (4-(4-(AMINOSULFONYL)PHENYL)-3-(3-HYDROXYPHENYL)-5-ISOXAZOLYL)METHYL

METABOLITE -> PARENT

Qualification:

URINE

Amount:

9 % (average)


					9TUW81Y3CE

PARECOXIB

PRODRUG -> METABOLITE ACTIVE

Amount:


					Y69WDQ5EHC

4-(5-METHYL-3-PHENYL-4-ISOXAZOLYL)BENZENESULFONIC ACID

METABOLITE -> PARENT

Qualification:

URINE

Amount:

[<0.5] % (average)

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Related Record

Type

Details


					2919279Q3W

VALDECOXIB

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Parameters
ORAL BIOAVAILABILITY	PHARMACOKINETIC	83 % (average)	ORAL ADMINISTRATION

Volume of Distribution	PHARMACOKINETIC	1.23 Liters/Kilogram (average)

Tmax	PHARMACOKINETIC	3 hours [1.5 to 4] (average)	ORAL ADMINISTRATION

Biological Half-life	PHARMACOKINETIC	[8 to 11] hours (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator