General Information of Drug (ID: DMRQAM0)

Drug Name
Phenacetin
Synonyms
phenacetin; 62-44-2; Acetophenetidin; N-(4-Ethoxyphenyl)acetamide; Acetphenetidin; Acetophenetidine; Acetophenetin; Phenacetine; p-Acetophenetidide; Contradouleur; Commotional; Achrocidin; Phenazetin; Contradol; Codempiral; 4'-Ethoxyacetanilide; 4-Ethoxyacetanilide; Acetamide, N-(4-ethoxyphenyl)-; p-Acetophenetidine; Fenacetina; Phenidin; Pyraphen; Phenacitin; Phenacetinum; Fenidina; Phenedina; Phenacet; Pertonal; Fenina; Phenin; Kalmin; p-Acetphenetidin; p-Acetophenetide; Phenazetina; Tetracydin; p-Ethoxyacetanilide; Stellacyl; Phenodyne; Imidazo[4,5-e][1,4]diazapine nucleotide (I)
Indication
Disease Entry ICD 11 Status REF
Analgesia MB40.8 Withdrawn from market [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 179.22
Topological Polar Surface Area (xlogp) 1.6
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Clearance
The drug present in the plasma can be removed from the body at the rate of 21 mL/min/kg [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 0.92 hours [4]
Metabolism
The drug is metabolized via the the body to paracetamol [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 278.98578 micromolar/kg/day [6]
Unbound Fraction
The unbound fraction of drug in plasma is 0.47% [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.4 L/kg [4]
Water Solubility
The ability of drug to dissolve in water is measured as 0.73 mg/mL [3]
Chemical Identifiers
Formula
C10H13NO2
IUPAC Name
N-(4-ethoxyphenyl)acetamide
Canonical SMILES
CCOC1=CC=C(C=C1)NC(=O)C
InChI
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)
InChIKey
CPJSUEIXXCENMM-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4754
ChEBI ID
CHEBI:8050
CAS Number
62-44-2
DrugBank ID
DB03783
TTD ID
D0O2IE
VARIDT ID
DR00653
INTEDE ID
DR1270

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TTL7C8Q IMDH1_HUMAN Inhibitor [7]
Prostaglandin G/H synthase 1 (COX-1) TT8NGED PGH1_HUMAN Inhibitor [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [9]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [9]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [10]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [11]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [12]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [11]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [13]
Cytochrome P450 2A13 (CYP2A13) DEXZA9U CP2AD_HUMAN Substrate [13]
Cholesterol 24-hydroxylase (CYP46A1) DEKP5HX CP46A_HUMAN Substrate [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Analgesia
ICD Disease Classification MB40.8
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Prostaglandin G/H synthase 1 (COX-1) DTT PTGS1 3.97E-03 0.16 0.43
Cytochrome P450 2A13 (CYP2A13) DME CYP2A13 9.89E-01 -6.41E-03 -3.83E-02
Cytochrome P450 2E1 (CYP2E1) DME CYP2E1 1.87E-04 -1.20E-01 -3.22E-01
Cholesterol 24-hydroxylase (CYP46A1) DME CYP46A1 1.79E-06 -3.32E-01 -6.53E-01
Cytochrome P450 2A6 (CYP2A6) DME CYP2A6 2.02E-01 -2.49E-02 -1.81E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.36E-01 1.62E-02 1.08E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 2.40E-01 -3.31E-02 -1.97E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 7.30E-01 -1.91E-02 -1.41E-01
Cytochrome P450 1A1 (CYP1A1) DME CYP1A1 6.83E-06 -1.42E-01 -4.93E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 1.90E-01 -9.81E-03 -5.96E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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2 An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987)Dubach UC1, Rosner B, St rmer T.Author information1Department of Internal Medicine, Kantonsspital, Basel, Switzerland.AbstractBACKGROUND: Phenacetin abuse is known to produce kidney disease; salicylate use is supposed to prevent cardiovascular disease. We conducted a prospective, longitudinal epidemiologic study to examine the effects of these drugs on cause-specific mortality and on cardiovascular morbidity.METHODS: In 1968 we evaluated a study group of 623 healthy women 30 to 49 years old who had evidence of a regular intake of phenacetin, as measured by urinary excretion of its metabolites, and a matched control group of 621 women. Salicylate excretion was also measured. All subjects were examined over a period of 20 years.RESULTS: Life-table analyses of mortality during the 20 years, with adjustment for the year of birth, cigarette smoking, and length of follow-up, revealed significant differences between the groups in overall mortality (study group vs. control group, 74 vs. 27 deaths; relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.3), deaths due to urologic or renal disease (relative risk, 16.1; 95 percent confidence interval, 3.9 to 66.1), deaths due to cancer (relative risk, 1.9; 95 percent confidence interval, 1.1 to 3.3), and deaths due to cardiovascular disease (relative risk, 2.9; 95 percent confidence interval, 1.5 to 5.5). The relative risk of cardiovascular disease (fatal or nonfatal myocardial infarction, heart failure, or stroke) was 1.8, and the 95 percent confidence interval 1.3 to 2.6. The odds ratio for the incidence of hypertension was 1.6, and the 95 percent confidence interval 1.2 to 2.1. The effects of phenacetin on morbidity and mortality, with adjustment for base-line salicylate excretion, were similar. In contrast, salicylate use had no effect on either mortality or morbidity.CONCLUSIONS: Regular use of analgesic drugs containing phenacetin is associated with an increased risk of hypertension and mortality and morbidity due to cardiovascular disease, as well as an increased riskof mortality due to cancer and urologic or renal disease. The use of salicylates carries no such risk.Comment inThe risks of phenacetin use. [N Engl J Med. 1991]PMID: 1984193 [PubMed - indexed for MEDLINE] Free full textSharePublication Types, MeSH Terms, SubstancesPublication TypesResearch Support, Non-U.S. Gov'tMeSH TermsAdultAgedAspirin/adverse effects*Cardiovascular Diseases/epidemiology*Cardiovascular Diseases/mortalityDose-Response Relationship, DrugFemaleHumansHypertension/epidemiologyKidney Diseases/mortalityLongitudinal StudiesMiddle AgedMortality*Neoplasms/mortalityPhenacetin/adverse effects*Prospective StudiesRiskSubstance-Related Disorders*Urologic Diseases/mortalitySubstancesPhenacetinAspirinLinkOut - more resourcesFull Text SourcesAtypon - PDFAtyponOvid Technologies, Inc.MedicalDrug Abuse - MedlinePlus Health InformationMiscellaneousACETYLSALICYLIC ACID - Hazardous Substances Data BankPHENACETIN - Hazardous Substances Data BankPubMed Commons home N Engl J Med. 1991 Jan 17;324(3):155-60.
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