LONAZOLAC

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H13ClN2O2
Molecular Weight	312.75
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC1=CN(N=C1C2=CC=C(Cl)C=C2)C3=CC=CC=C3

InChI

InChIKey=XVUQHFRQHBLHQD-UHFFFAOYSA-N

InChI=1S/C17H13ClN2O2/c18-14-8-6-12(7-9-14)17-13(10-16(21)22)11-20(19-17)15-4-2-1-3-5-15/h1-9,11H,10H2,(H,21,22)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3864763 | https://www.ncbi.nlm.nih.gov/pubmed/1693604 | https://www.ncbi.nlm.nih.gov/pubmed/2370919 | https://www.epharmapedia.com/medicine/profile/182361/Iritren.html?lang=en&tab=druginfo

Lonazolac is a nonsteroidal anti-inflammatory drug. The mononuclear cell response to a synovial stimulus can be abolished by very low concentrations of lonazolac. This blockade can be completely released by the addition of prostaglandin E2. Lonazolac appears therefore as an agent able in addition to modulate the immune response. The release of histamine from human basophils was significantly decreased after preincubation of the cells with lonazolac Ca. Preincubation of human polymorphonuclear leukocytes with lonazolac Ca led to an inhibition of leukotriene generation induced by either the Ca ionophore or opsonized zymosan. Lonazolac Ca affected different enzymes of the platelet activating factor metabolism. After pre- and post-treatment with lonazolac-Ca, the numbers of animals with lung metastases and the score of metastases significantly decreased. Lonazolac-Ca is indicated for the treatment of painful inflammatory rheumatic diseases of the joints and the spine. Acute irritation in osteoarthritis and spondylosis. Soft tissue rheumatism. Post-traumatic and postoperative pain and swelling states.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 2B1 6 Target ID: CHEMBL3335 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1650212	Substrate 661
Cytochrome P450 2A1 1 Target ID: CHEMBL3509602 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1650212	Substrate 661
Cytochrome P450 2E1 25 Target ID: CHEMBL5978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1650212	Substrate 661
platelet activating factor production involved in inflammatory response 1 Target ID: GO:0002391 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1693604	Modulator 846
regulation of leukotriene production involved in inflammatory response 1 Target ID: GO:0035490 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1693604	Inhibitor 8504
histamine production involved in inflammatory response 1 Target ID: GO:0002349 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1693604	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Synovitis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9726694	Palliative	Not Provided 511	Irritren Approved Use Unknown
Rheumatoid arthritis 320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3246140 https://www.ncbi.nlm.nih.gov/pubmed/6350135 https://www.ndrugs.com/?s=irritren	Palliative	Approved 8583	Irritren Approved Use Indicated for the treatment of painful inflammatory rheumatic diseases of the joints and the spine. Acute irritation in osteoarthritis and spondylosis. Soft tissue rheumatism. Post-traumatic and postoperative pain and swelling states.
Osteoarthritis 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7048748 https://www.ndrugs.com/?s=irritren	Palliative	Approved 8583	Irritren Approved Use Indicated for the treatment of painful inflammatory rheumatic diseases of the joints and the spine. Acute irritation in osteoarthritis and spondylosis. Soft tissue rheumatism. Post-traumatic and postoperative pain and swelling states.

C_max

Value	Dose	Co-administered	Analyte	Population
1.8 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9726694/	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LONAZOLAC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9726694/	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LONAZOLAC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	substrate 1193 inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 CYP2C19 2057 P-gp 1741 CYP1A2 2153 CYP19A1 429	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 8.0	inconclusive [IC50 43.6486 uM]
BCRP 985	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 26.0	no
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 188.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 245.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 240.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 217.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 236.0	no
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 27.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 2.0	yes [IC50 4.3649 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 216 \| 217	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11824818/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/68706#section=Biological-Test-Results Page: 146.0

PubMed

Title	Date	PubMed
Determination of lonazolac and its hydroxy and O-sulfated metabolites by on-line sample preparation liquid chromatography with fluorescence detection.	2002-01-25	11824818
Screening procedure for detection of non-steroidal anti-inflammatory drugs and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation.	2001-06-02	11386636
Transsynovial kinetics of lonazolac and its hydroxy metabolite in synovitis patients.	1998-08	9726694
Perifusion of co-cultured hepatocytes: optimization of studies on drug metabolism and cytotoxicity in vitro.	1996-04	8738475
[Gastroduodenal tolerance and clinical effectiveness of therapy with lonazolac-calcium in rheumatic diseases].	1996	9045528
Different drug metabolizing capacities in cultured periportal and pericentral hepatocytes.	1994-08-17	8080449
The H+, K(+)-ATPase inhibitor pantoprazole (BY1023/SK&F96022) interacts less with cytochrome P450 than omeprazole and lansoprazole.	1991-07-05	1650212
Effects of the nonsteroidal anti-inflammatory compounds Lonazolac Ca, indomethacin and NDGA on inflammatory mediator generation and release from various cells.	1990-03-01	1693604
Pharmacokinetics of small unilamellar liposomes and incorporated lonazolac after i.m. administration.	1990-01-01	2308057
Reductive effect of lonazolac on lung metastasis formation in mice.	1990	2370919
A double-blind parallel group comparative study of lonazolac-calcium and diclofenac in patients with rheumatoid arthritis.	1988-12	3246140
Blocking of mononuclear cell activation by lonazolac.	1985	3864763
[Lonazolac - a new non-steroidal antirheumatic agent. Report of a double-blind crossover clinical study].	1983-06	6350135
[Synthesis and physico-chemical properties of lonazolac-Ca, a new antiphlogistic/antirheumatic agent].	1981	6972771
[Lonazolac-Ca = Calcium [3-(p-chlorophenyl)-1-phenylpyrazole-4[ -acetate 1 Pharmacological properties of a new antiinflammatory/antirheumatic drug (author's transl)].	1981	6972772

Patents

Sample Use Guides

In Vivo Use Guide

300 mg taken twice daily

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

LONAZOLAC

Official Name

English

LONAZOLAC CALCIUM SALT

Preferred Name

English

NSC-319772

Code

English

3-(P-CHLOROPHENYL)-1-PHENYLPYRAZOLE-4-ACETIC ACID

Common Name

English

lonazolac [INN]

Common Name

English

Lonazolac [WHO-DD]

Common Name

English

LONAZOLAC [MI]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QM01AB09