ZOMEPIRAC

First approved in 1980

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H14ClNO3
Molecular Weight	291.73
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(CC(O)=O)=CC(C)=C1C(=O)C2=CC=C(Cl)C=C2

InChI

InChIKey=ZXVNMYWKKDOREA-UHFFFAOYSA-N

InChI=1S/C15H14ClNO3/c1-9-7-12(8-13(18)19)17(2)14(9)15(20)10-3-5-11(16)6-4-10/h3-7H,8H2,1-2H3,(H,18,19)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7018870 | https://www.ncbi.nlm.nih.gov/pubmed/7241789 | https://www.drugbank.ca/drugs/DB04828 | https://www.ncbi.nlm.nih.gov/pubmed/7044754

Zomepirac Sodium (Zomax) is a pyrrole-acetic acid structurally related to tolmetin sodium. Zomepirac is a prostaglandin synthetase inhibitor and is not an opioid, an opioid antagonist, or a salicylate. Zomepirac was approved by the Food and Drug Administration for marketing in the United States as an analgesic. It was indicated for all forms of mild to moderately severe pain, and was being promoted as a "comprehensive, non-addicting analgesic." Later Zomepirac was found to be associated with fatal and near-fatal anaphylactoid reactions. The manufacturer voluntarily removed Zomax tablets from the Canadian, US, and UK markets in March 1983.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase 89 Target ID: CHEMBL2096674 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7018870	Inhibitor 8297		15.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7018870 https://www.ncbi.nlm.nih.gov/pubmed/6776300	Primary		Withdrawn	ZOMAX Approved Use ZOMAX is indicated for all forms of mild to moderately severe pain. Launch Date 1979

C_max

Value	Dose	Analyte	Population
7.94 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7357796	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOMEPIRAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.42 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7357796	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOMEPIRAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.47 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7357796	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOMEPIRAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1102.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7357796	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOMEPIRAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
494.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7357796	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOMEPIRAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
232.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7357796	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ZOMEPIRAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
100 mg 6 times / day multiple, oral Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6222714	unhealthy, 28 years n = 1 Health Status: unhealthy Age Group: 28 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6222714	Disc. AE: Renal insufficiency... AEs leading to discontinuation/dose reduction: Renal insufficiency (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6222714
300 mg 1 times / day multiple, oral Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6222714	unhealthy, 36-72 years n = 2 Health Status: unhealthy Age Group: 36-72 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/6222714	Disc. AE: Renal insufficiency... AEs leading to discontinuation/dose reduction: Renal insufficiency (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/6222714
800 mg 1 times / day single, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6883915	unhealthy n = 10 Health Status: unhealthy Condition: opioid abuse Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/6883915	Other AEs: Backache, Nausea... Other AEs: Backache (2 patients) Nausea (2 patients) Churning of stomach (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/6883915

AEs

AE	Significance	Dose	Population
Renal insufficiency	1 patient Disc. AE	100 mg 6 times / day multiple, oral Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6222714	unhealthy, 28 years n = 1 Health Status: unhealthy Age Group: 28 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6222714
Renal insufficiency	2 patients Disc. AE	300 mg 1 times / day multiple, oral Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6222714	unhealthy, 36-72 years n = 2 Health Status: unhealthy Age Group: 36-72 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/6222714
Backache	2 patients	800 mg 1 times / day single, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6883915	unhealthy n = 10 Health Status: unhealthy Condition: opioid abuse Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/6883915
Churning of stomach	2 patients	800 mg 1 times / day single, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6883915	unhealthy n = 10 Health Status: unhealthy Condition: opioid abuse Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/6883915
Nausea	2 patients	800 mg 1 times / day single, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6883915	unhealthy n = 10 Health Status: unhealthy Condition: opioid abuse Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/6883915

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587		substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054 CYP2C8 693 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16251255/ Page: 6.0	no

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16251255/ Page: 3.0	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16251255/ Page: 3.0	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16251255/ Page: 3.0	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16251255/ Page: 3.0	no
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16251255/ Page: 6.0	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-044091	http://www.3bsc.com/index/pro_info.php?id=76290
AA Blocks	AA003VCA	https://www.aablocks.com/goods/Goods/detail?id=AA003VCA
AHH Chemical co.,ltd	MT-60607	http://www.ahhchemical.com/product/MT-60607.html
AbMole Bioscience	M6067	http://www.abmole.com/products/zomepirac-sodium-salt.html
Ambinter	Amb10843649	http://www.ambinter.com/reference/10843649
Ambinter	Amb22352686	http://www.ambinter.com/reference/22352686
Angel Pharmatech	AG302903	http://www.angelpharmatech.com/64092-48-4.html
Aurora Fine Chemicals LLC	A06.999.444	http://online.aurorafinechemicals.com/info?ID=A06.999.444
Aurora Fine Chemicals LLC	A17.913.073	http://online.aurorafinechemicals.com/info?ID=A17.913.073
BOC Sciences	33369-31-2	https://www.bocsci.com/zomepirac-cas-33369-31-2-item-109159.html
BOC Sciences	64092-48-4	https://www.bocsci.com/zomepirac-sodium-cas-64092-48-4-item-74212.html
Chem Scene	CS-4353	http://www.chemscene.com/64092-48-4.html
ChemMol	30106032	http://www.chemmol.com/chemmol/30106032.html
ChemMol	99071483	http://www.chemmol.com/chemmol/99071483.html
ChemMol	99123860	http://www.chemmol.com/chemmol/99123860.html
Chemspace	CSSB00000078942	https://chem-space.com/CSSB00000078942
Debye Scientific	DA-06775	http://www.debyesci.com/cas_33369-31-2.html
Finetech	FT-0708860	http://www.finetechnology-ind.com/prod/detail/pub/33369-31-2.html
Finetech	FT-0675929	http://www.finetechnology-ind.com/prod/detail/pub/64092-48-4.html
Glentham Life Sciences	GP8300	http://www.glentham.com/products/product/GP8300/
MedChem Express	HY-B0890	https://www.medchemexpress.com/Zomepirac-sodium-salt.html
MolPort	MolPort-005-936-008	https://www.molport.com/shop/molecule-link/MolPort-005-936-008
Molcore	MC549251	https://www.molcore.com/product/33369-31-2
Molcore	MC565048	https://www.molcore.com/product/64092-48-4
MuseChem	I004423	https://www.musechem.com/product/I004423.html
Sigma-Aldrich	Z2625_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/z2625?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S573360	https://www.smolecule.com/products/s573360
Yuhao Chemical	RT2519	http://www.chemyuhao.com/64092-48-4.html
mcule	MCULE-3654355863	https://mcule.com/MCULE-3654355863/

PubMed

Title	Date	PubMed
Clinical analgesic assay of oral zomepirac and intramuscular morphine.	1979	121342
Long-term safety of zomepirac: a double-blind comparison with aspirin in patients with osteoarthritis.	1980 May-Jun	6995502
Orally administered zomepirac and parenterally administered morphine. Comparison for the treatment of postoperative pain.	1980 Nov 21	6776300
Anaphylactic shock, acute renal failure, and disseminated intravascular coagulation. Suspected complications of zomepirac.	1982 Feb 26	7057609
Reversible nonoliguric acute renal failure associated with zomepirac therapy.	1982 Jun	7078269
Zomepirac, interstitial nephritis, and renal failure.	1982 Sep	7114649
Nonoliguric renal failure associated with zomepirac.	1983 Apr 1	6827751
Zomepirac-related acute renal failure.	1983 Jan	6825559
Renal failure and tubular dysfunction due to zomepirac therapy.	1983 Jan 21	6848832
Influence of uremia, hemodialysis, and nonesterified fatty acids on zomepirac plasma protein binding.	1983 Nov	6627828
Long-term therapy for the pain of osteoarthritis: a comparison of zomepirac sodium and aspirin.	1983 Nov-Dec	6363464
A zomepirac reaction mimicking ectopic pregnancy.	1984 Jun	6734436
Focal renal cortical necrosis associated with zomepirac.	1984 Jun	6731466
Interstitial nephritis and proteinuria associated with zomepirac.	1984 Mar-Apr	6723230
Zomepirac-induced anaphylactic shock: an under-reported phenomenon.	1985 Oct	4073114
Reinduction of the hypnotic effects of thiopental with NSAIDs by decreasing thiopental plasma protein binding in humans.	1993 Apr	8517101
Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs.	1993 Jan	8423545
Reversible binding of tolmetin, zomepirac, and their glucuronide conjugates to human serum albumin and plasma.	1994 Feb	8027947
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.	2001 Jan 10	11231885
Dipeptidyl peptidase IV is a target for covalent adduct formation with the acyl glucuronide metabolite of the anti-inflammatory drug zomepirac.	2001 Jan 5	11205870
Inhibition of proliferation of HT-29 colon adenocarcinoma cells by carboxylate NSAIDs and their acyl glucuronides.	2001 Nov 21	11764005
HPLC/1H NMR spectroscopic studies of the reactive alpha-1-O-acyl isomer formed during acyl migration of S-naproxen beta-1-O-acyl glucuronide.	2001 Oct	11599927
India ink staining after sodium dodecyl sulfate polyacrylamide gel electrophoresis and in conjunction with Western blots for peptide mapping by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.	2002	11754245
Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouse.	2002 Jan	11895555
Differential binding mode of diverse cyclooxygenase inhibitors.	2002 Mar	11885959
Investigating the TNP-OVA and direct popliteal lymph node assays for the detection of immunostimulation by drugs associated with anaphylaxis in humans.	2002 May-Jun	12015798
Identification of zomepirac-S-acyl-glutathione in vitro in incubations with rat hepatocytes and in vivo in rat bile.	2003 Nov	14570776
Photolysis of NSAIDs. IV. Photoproducts of zomepirac determined by LC-ESI-MS.	2004 Dec	15386573
Evaluation of a lymph node proliferation assay for its ability to detect pharmaceuticals with potential to cause immune-mediated drug reactions.	2005 Jan 1	18958655
Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2.	2005 Mar	15563582
In vitro and in vivo studies on acyl-coenzyme A-dependent bioactivation of zomepirac in rats.	2005 Nov	16300382
I almost crossed over.	2005 Oct	17094512
ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.	2005 Oct 4	16202168
Pharmaceutical quality control of acid and neutral drugs based on competitive self-assembly in amphiphilic systems.	2006 Jan	16365667
Evidence for the bioactivation of zomepirac and tolmetin by an oxidative pathway: identification of glutathione adducts in vitro in human liver microsomes and in vivo in rats.	2006 Jan	16251255
A simple in vitro model to study the stability of acylglucuronides.	2007 Jan-Feb	16713308
Determination of degradation pathways and kinetics of acyl glucuronides by NMR spectroscopy.	2007 Jun	17536843
Clinical management of adult patients with a history of nonsteroidal anti-inflammatory drug-induced urticaria/angioedema: update.	2007 Mar 15	20525150
The effects of etodolac, nimesulid and naproxen sodium on the frequency of sister chromatid exchange after enclused third molars surgery.	2008 Oct 31	18972594
The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol.	2010 Jul 5	20602760
Downstream gene activation of the receptor ALX by the agonist annexin A1.	2010 Sep 17	20862244

Patents

Sample Use Guides

In Vivo Use Guide

The oral dose of zomepirac for mild to moderately severe pain is 50-100 mg every four to six hours. In acute moderate to severe pain in adults, a 100-mg dose would be reasonable initial therapy. In chronic pain situations, the 50-mg dose may be as effective in some patients as the 100-mg dose. Doses of more than 100 mg are not recommended.

Route of Administration: Oral

In Vitro Use Guide

Zomepirac failed to displace tritiated etorphine significantly at concentrations up to 200 umol/l. It was active (3-7 X 10(-5) mol/l) on both the electrically stimulated guinea pig ileum and mouse vas deferens but was less efficacious than morphine; these effects were not reversed by narcotic antagonists.

Name

Type

Language

ZOMEPIRAC

Official Name

English

Zomepirac [WHO-DD]

Common Name

English

zomepirac [INN]

Common Name

English

ZOMEPIRAC [MI]

Common Name

English

Classification Tree Code System Code

WHO-ATC

M01AB04