PHENACETIN

US Previously Marketed

First marketed in 1887

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H13NO2
Molecular Weight	179.2157
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=CC=C(NC(C)=O)C=C1

InChI

InChIKey=CPJSUEIXXCENMM-UHFFFAOYSA-N

InChI=1S/C10H13NO2/c1-3-13-10-6-4-9(5-7-10)11-8(2)12/h4-7H,3H2,1-2H3,(H,11,12)

HIDE SMILES / InChI

Molecular Formula	C10H13NO2
Molecular Weight	179.2157
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/books/NBK304337
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18140117 | https://www.ncbi.nlm.nih.gov/pubmed/3552585 | https://www.ncbi.nlm.nih.gov/pubmed/12242329 | https://www.ncbi.nlm.nih.gov/pubmed/14592552

Phenacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years. Since a major portion of a dose of phenacetin is rapidly metabolised to paracetamol, it seems possible that phenacetin owes some of its therapeutic activity to its main metabolite, paracetamol, whereas its most troublesome side effect (methaemoglobinaemia) is due to another metabolite, p-phenetidine. Phenacetin was shown to inhibit cyclooxygenase (COX)-3, a cyclooxygenase-1 variant while p-phenetidine potently inhibits both COX-1 and COX-2. There is sufficient evidence in humans for the carcinogenicity of analgesic mixtures containing phenacetin. Analgesic mixtures containing phenacetin cause cancer of the renal pelvis, and of the ureter. Phenacetin was withdrawn from many analgesic mixtures long before the legal ban in several countries.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Prostaglandin G/H synthase 1 30 Target ID: Q8HZR1 Gene ID: 403544.0 Gene Symbol: PTGS1 Target Organism: Canis lupus familiaris (Dog) (Canis familiaris) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12242329	Inhibitor 8297	102.0 µM [IC50]
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14592552	Inhibitor 8297
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14592552	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/books/NBK304337 https://www.ncbi.nlm.nih.gov/pubmed/3552585	Primary		Withdrawn	Phenacetin Approved Use Phenacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years. Launch Date 1886

C_max

Value	Dose	Analyte	Population
6.9 μg/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	ACETAMINOPHEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13.5 μg/mL EXPERIMENT https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/j.1552-4604.1974.tb02323.x	1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.48 μg/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.84 μg/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.5 μg/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
40.4 μg × h/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	ACETAMINOPHEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
20.72 μg × h/mL EXPERIMENT https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/j.1552-4604.1974.tb02323.x	1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.58 μg × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.84 μg × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.3 μg × h/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
2.6 h EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	ACETAMINOPHEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.6 h EXPERIMENT https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/j.1552-4604.1974.tb02323.x	1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.98 h EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.1 h EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.9 h EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23607050/			PHENACETIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1.5 g 1 times / day multiple, oral Studied dose Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/	unhealthy, 34 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 34 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/	Other AEs: Nephropathy... Other AEs: Nephropathy Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/
250 mg multiple, oral Studied dose Dose: 250 mg Route: oral Route: multiple Dose: 250 mg Co-administed with:: acetylsalicylic acid(250 mg; 40 years) codeine phosphate(10 mg; 40 years) Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/	unhealthy, 54 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 54 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/	Other AEs: Nephropathy... Other AEs: Nephropathy Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/
1 g 1 times / day multiple, oral Studied dose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/831357/	unhealthy, 56 years n = 1 Health Status: unhealthy Condition: knee pain Age Group: 56 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/831357/	Other AEs: Transitional cell carcinoma... Other AEs: Transitional cell carcinoma Sources: https://pubmed.ncbi.nlm.nih.gov/831357/
625 mg 1 times / day multiple, oral (mean) Studied dose Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/	unhealthy, 85 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 85 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/	Other AEs: Urothelial carcinoma... Other AEs: Urothelial carcinoma Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/
0.9 g 4 times / day multiple, oral Studied dose Dose: 0.9 g, 4 times / day Route: oral Route: multiple Dose: 0.9 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/	healthy, age 18 to 44 years n = 10 Health Status: healthy Age Group: age 18 to 44 years Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/	Other AEs: Nephritis NEC... Other AEs: Nephritis NEC (20%) Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/

AEs

AE	Significance	Dose	Population
Nephropathy		1.5 g 1 times / day multiple, oral Studied dose Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/	unhealthy, 34 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 34 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/
Nephropathy		250 mg multiple, oral Studied dose Dose: 250 mg Route: oral Route: multiple Dose: 250 mg Co-administed with:: acetylsalicylic acid(250 mg; 40 years) codeine phosphate(10 mg; 40 years) Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/	unhealthy, 54 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 54 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/
Transitional cell carcinoma		1 g 1 times / day multiple, oral Studied dose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/831357/	unhealthy, 56 years n = 1 Health Status: unhealthy Condition: knee pain Age Group: 56 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/831357/
Urothelial carcinoma		625 mg 1 times / day multiple, oral (mean) Studied dose Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/	unhealthy, 85 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 85 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/
Nephritis NEC	20%	0.9 g 4 times / day multiple, oral Studied dose Dose: 0.9 g, 4 times / day Route: oral Route: multiple Dose: 0.9 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/	healthy, age 18 to 44 years n = 10 Health Status: healthy Age Group: age 18 to 44 years Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054 CYP2E1 667 CYP1A1 349 CYP2C19 991

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP1A2 1054	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC298137/pdf/pnas00287-0044.pdf#page=1 Page: 1.0	major	yes (co-administration study) Comment: cigarette smoking induced CYP1A2 and increased O-deethylase activity Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC298137/pdf/pnas00287-0044.pdf#page=1 Page: 1.0
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10627170/ Page: 1.0	minor
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	minor

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8050	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8050
ChemicalBook	CB44796969	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB44796969
ChemicalBook	CB6141828	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6141828
MolPort	MolPort-000-626-710	https://www.molport.com/shop/molecule-link/MolPort-000-626-710
Selleck Chemicals	phenacetin	http://www.selleckchem.com/products/phenacetin.html
ZINC	ZINC000000000602	http://zinc15.docking.org/substances/ZINC000000000602
eMolecules	490668	https://www.emolecules.com/cgi-bin/more?vid=490668

PubMed

Title	Date	PubMed
Letter: The clinical course of patients with analgesic nephropathy.	1975 Aug 9	1139519
The radiological diagnosis of analgesic nephropathy.	1975 Jul	1201638
Role of CYP1A2 in the toxicity of long-term phenacetin feeding in mice.	1999 Jul	10445756
Regular use of analgesics is a risk factor for renal cell carcinoma.	1999 Oct	10507783
Epidemiology and etiology of premalignant and malignant urothelial changes.	2000	11144890
The syrian hamster embryo (SHE) cell transformation assay: review of the methods and results.	2001	11695550
Neonatal mouse model: review of methods and results.	2001	11695548
Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism.	2001 Apr 17	11292550
Role of cytochrome P450 isoenzymes in metabolism of O(6)-benzylguanine: implications for dacarbazine activation.	2001 Dec	11751525
Relationship between nonphenacetin-combined analgesics and nephropathy.	2001 Jun	11409383
Relationship between nonphenacetin-combined analgesics and nephropathy.	2001 Jun	11409381
Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline.	2001 Mar	11465391
Suppression of agglomeration in fluidized bed coating. IV. Effects of sodium citrate concentration on the suppression of particle agglomeration and the physical properties of HPMC film.	2001 Mar 14	11250087
Optimization of an exogenous metabolic activation system for FETAX. II. Preliminary evaluation.	2001 May	11360430
[Analgesics-induced chronic renal failure in patients on dialysis therapy in Hungary].	2001 May 13	11419294
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
[Etiopathology, risk factors, environmental influences and epidemiology of bladder cancer].	2001 Nov	11760347
[Optimal conditions for extraction of "caffetin" and "saridon" tablet components from aqueous solutions].	2001 Nov-Dec	11871327
Renal PGE2 production in the human and rat following phenacetin, acetaminophen and p-aminophenol.	2002	14632321
In vivo effect of diallyl sulfide and cimetidine on phenacetin metabolism and bioavailability in rat.	2002	12136947
Phenacetin O-deethylation in extrahepatic tissues of rats.	2002 Apr-Jun	12064368
Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method.	2002 Aug	12124306
Validated HPLC method for determination of chlorzoxazone in human serum and its application in a clinical pharmacokinetic study.	2002 Dec	12561241
Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat.	2002 Mar 1	11911841
PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690].	2002 Mar 27	11918829
Phenotype of CYP2C19 and CYP3A4 by determination of omeprazole and its two main metabolites in plasma using liquid chromatography with liquid-liquid extraction.	2002 Nov 25	12401374
Polymer particle erosion controlling drug release. II. Swelling investigations to clarify the release mechanism.	2002 Oct 24	12429482
Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.	2003 Dec 9	14640697
Identification of cytochrome P450 1A2 as enzyme involved in the microsomal metabolism of Huperzine A.	2003 Feb 14	12586202
Simultaneous liquid chromatography-tandem mass spectrometric determination of albendazole sulfoxide and albendazole sulfone in plasma.	2003 Jan 5	12450544
HPLC analyses and pharmacokinetic studies of baicalin and oxymatrine in rabbits.	2003 Sep	14531454
Induction of diphenytriazol on cytochrome CYP1A.	2004 Apr	15066225
Analgesic nephropathy in Hungary: the HANS study.	2004 Apr	15031338
Phenacetin and cocaine in a body packer.	2004 Apr 20	15066715
Interaction of cyclooxygenase isoenzymes, nitric oxide, and afferent neurons in gastric mucosal defense in rats.	2004 Jan	14569068
Evaluation of the patient with hematuria.	2004 Mar	15049581

Patents

Sample Use Guides

In Vivo Use Guide

Analgesic mixtures containing phenacetin were previously marketed as tablets or capsules containing between 150 and 300 mg phenacetin. Common combinations were: 150 mg phenacetin, 230 mg aspirin, and 15 or 30 mg caffeine; or 150 mg phenacetin, 230 mg aspirin, 30 mg caffeine, and 8, 15, 30, or 60 mg codeine phosphate. Phenacetin alone was also available in 250 and 300 mg doses as tablets, and up to 500 mg doses as powder. The usual dose was 300 mg 4–6 times per day, and the daily dose was not to exceed 2 g

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:05:26 GMT 2023` Edited by `admin` on `Fri Dec 15 15:05:26 GMT 2023`
Record UNII	ER0CTH01H9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PHENACETIN

Official Name

English

PHENACETIN [VANDF]

Common Name

English

4-ETHOXY-1-ACETYLAMINOBENZENE

Systematic Name

English

FENIDINA

Common Name

English

NSC-7651

Code

English

PHENACETIN [MART.]

Common Name

English

ACETAMIDE, N-(4-ETHOXYPHENOL)-

Common Name

English

PHENACETIN [JAN]

Common Name

English

ACETPHENETIDIN

Common Name

English

KALMIN

Common Name

English

PHENACETIN [INCI]

Common Name

English

PHENACETIN MELTING POINT STANDARD

Common Name

English

PHENACETIN [MI]

Common Name

English

PHENACETINUM

Common Name

English

PHENACETINUM [HPUS]

Common Name

English

PHENACETIN [USP-RS]

Common Name

English

PHENACETIN [IARC]

Common Name

English

PHENAZETIN

Common Name

English

phenacetin [INN]

Common Name

English

P-ACETOPHENETIDIDE

Common Name

English

Phenacetin [WHO-DD]

Common Name

English

PHENACETIN [HSDB]

Common Name

English

ACETOPHENETIDIN

Common Name

English

Classification Tree Code System Code

WHO-ATC

N02BE53