PHENACETIN

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

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

Description

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 Phenacetin was withdrawn from many analgesic mixtures long before the legal ban in several countries.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	Inhibitor 8,504	102.0 µM [IC50]
Cyclooxygenase-1 131	Inhibitor 8,504
Cyclooxygenase-2 201	Inhibitor 8,504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619	Primary		Withdrawn	Phenacetin

C_max

Value	Dose	Analyte	Population
13.5 μg/mL	1.5 g single, oral	PHENACETIN plasma	Homo sapiens
2.5 μg/mL	900 mg single, oral	PHENACETIN plasma	Homo sapiens
6.9 μg/mL	900 mg single, oral	ACETAMINOPHEN plasma	Homo sapiens
1.84 μg/mL	900 mg single, oral	PHENACETIN plasma	Homo sapiens
1.48 μg/mL	900 mg single, oral	PHENACETIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
20.72 μg × h/mL	1.5 g single, oral	PHENACETIN plasma	Homo sapiens
5.3 μg × h/mL	900 mg single, oral	PHENACETIN plasma	Homo sapiens
40.4 μg × h/mL	900 mg single, oral	ACETAMINOPHEN plasma	Homo sapiens
1.84 μg × h/mL	900 mg single, oral	PHENACETIN plasma	Homo sapiens
1.58 μg × h/mL	900 mg single, oral	PHENACETIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
0.6 h	1.5 g single, oral	PHENACETIN plasma	Homo sapiens
0.9 h	900 mg single, oral	PHENACETIN plasma	Homo sapiens
2.6 h	900 mg single, oral	ACETAMINOPHEN plasma	Homo sapiens
1.1 h	900 mg single, oral	PHENACETIN plasma	Homo sapiens
0.98 h	900 mg single, oral	PHENACETIN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
70%			PHENACETIN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1.5 g 1 times / day multiple, oral Studied dose	unhealthy, 34 years	Other AEs: Nephropathy...
250 mg multiple, oral Studied dose	unhealthy, 54 years	Other AEs: Nephropathy...
1 g 1 times / day multiple, oral Studied dose	unhealthy, 56 years	Other AEs: Transitional cell carcinoma...
625 mg 1 times / day multiple, oral Studied dose	unhealthy, 85 years	Other AEs: Urothelial carcinoma...
0.9 g 4 times / day multiple, oral Studied dose	healthy, age 18 to 44 years	Other AEs: Nephritis NEC...

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AEs

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AE	Significance	Dose	Population
Nephropathy		1.5 g 1 times / day multiple, oral Studied dose	unhealthy, 34 years
Nephropathy		250 mg multiple, oral Studied dose	unhealthy, 54 years
Transitional cell carcinoma		1 g 1 times / day multiple, oral Studied dose	unhealthy, 56 years
Urothelial carcinoma		625 mg 1 times / day multiple, oral Studied dose	unhealthy, 85 years
Nephritis NEC	20%	0.9 g 4 times / day multiple, oral Studied dose	healthy, age 18 to 44 years

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946	substrate 1,193	substrate 1,388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1,197 CYP2E1 729 CYP1A1 389 CYP2C19 1,119

Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP1A1 389	substrate 4,014	inconclusive
CYP2C19 1,119	substrate 4,014	inconclusive
CYP2D6 1,388	substrate 4,014	inconclusive
CYP3A4 1,946	substrate 4,014	inconclusive
CYP1A2 1,197	substrate 4,014	major	yes (co-administration study)

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Sourcing

Sourcing

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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
eMolecules	490668	https://www.emolecules.com/cgi-bin/more?vid=490668
MolPort	MolPort-000-626-710	https://www.molport.com/shop/molecule-link/MolPort-000-626-710

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PubMed

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Title	Date	PubMed
IS PHENACETIN A NEPHROTOXIN?A REPORT ON TWENTY-THREE USERS OF THE DRUG.	1964 Aug	14180501
Role of CYP1A2 in the toxicity of long-term phenacetin feeding in mice.	1999 Jul	10445756
A population approach to enzyme characterization and identification: application to phenacetin O-deethylation.	2000 Dec	11303964
[Simultaneous determination of aspirin, phenacetin and caffeine in compound APC by derivative ratio UV adsorption spectrum method].	2001 Aug	12945285
A rapid reversed phase high performance liquid chromatographic method for determination of etoposide (VP-16) in human plasma.	2001 Jun	11377013

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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

Show entries

Name

Type

Language

PHENACETIN

Official Name

English

PHENACETINUM

Preferred Name

English

PHENACETIN [VANDF]

Common Name

English

4-ETHOXY-1-ACETYLAMINOBENZENE

Systematic Name

English

FENIDINA

Common Name

English

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Classification Tree

Code System

Code

Anilides

WHO-ATC

N02BE53

Subpart B--Compounded Drug Products

CFR

21 CFR 216.24

Anilides

WHO-VATC

QN02BE53

Anilides

WHO-ATC

N02BE03

Anilides

WHO-VATC

QN02BE73

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Code System

Code

Type

Description

EVMPD

SUB09745MIG

PRIMARY

IUPHAR

7402

PRIMARY

CAS

62-44-2

PRIMARY

CHEBI

8050

PRIMARY

FDA UNII

ER0CTH01H9

PRIMARY

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ACTIVE MOIETY


					ER0CTH01H9

PHENACETIN

METABOLITE ACTIVE (PARENT)


					362O9ITL9D

Acetaminophen

METABOLITE TOXIC (PARENT)


					9TSL224ZSE

P-PHENETIDINE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound