General Information of Drug (ID: DR0037)
Drug Name
Acetaminophen
Synonyms
Acetaminofen; Algotropyl; Alvedon; Anaflon; Anelix; Apamide; Clixodyne; Datril; Dymadon; Febridol; Febrilix; Febrolin; Finimal; Gelocatil; Homoolan; Injectapap; Lestemp; Liquagesic; Lonarid; Multin; N-(4-Hydroxyphenyl)acetamide; N-Acetyl-p-aminophenol; Naprinol; Panadol; Paracet; Paracetamol; Pyrinazine; Servigesic; Tabalgin; Tralgon; Tussapap; Tylenol; Valadol; Valgesic; acetaminophen; p-Acetamidophenol; p-Acetaminophenol; p-Hydroxyacetanilide; 103-90-2; 4'-Hydroxyacetanilide; 4-Acetamidophenol; APAP; Abensanil; Acamol; Acenol; Acetagesic; Acetalgin
Indication Anaesthesia [ICD11: 8E22] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 151.16 Topological Polar Surface Area 49.3
Heavy Atom Count 11 Rotatable Bond Count 1
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
1983
PubChem SID
9023 ; 70391 ; 408305 ; 609360 ; 3131814 ; 4266416 ; 5199969 ; 7847284 ; 7890920 ; 7978634 ; 8149184 ; 8151363 ; 10321115 ; 10502811 ; 11112253 ; 11114188 ; 11335835 ; 11361074 ; 11362770 ; 11365332 ; 11367894 ; 11371386 ; 11373699 ; 11376056 ; 11462046 ; 11466896 ; 11468016 ; 11483746 ; 11486572 ; 11487901 ; 11490099 ; 11491955 ; 11493830 ; 11532417 ; 15321628 ; 17390068 ; 17436465 ; 22388563 ; 24714721 ; 24715004 ; 24890717 ; 24890930 ; 24891173 ; 24891200 ; 26512241 ; 26611588 ; 26679279 ; 26697092 ; 26747171 ; 26752236
ChEBI ID
ChEBI:46195
CAS Number
103-90-2
TTD Drug ID
D0U5QK
Formula
C8H9NO2
Canonical SMILES
CC(=O)NC1=CC=C(C=C1)O
InChI
1S/C8H9NO2/c1-6(10)9-7-2-4-8(11)5-3-7/h2-5,11H,1H3,(H,9,10)
InChIKey
RZVAJINKPMORJF-UHFFFAOYSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Acetaminophen glucuronide DM000606
83944
Conjugation - Glucuronidation 1 [10] , [18] , [19]
Acetaminophen sulfate DM000607
83939
Conjugation - Sulfation 1 [10] , [18] , [19]
NAPQI DM002758
39763
Oxidation - Oxidation 1 [20] , [21]
Acetaminophen cysteine DM000605
83997
Conjugation - Conjugation 2 [10] , [22] , [18]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000048 Acetaminophen Acetaminophen glucuronide Conjugation - Glucuronidation UGT2B15 ... [10], [18], [19]
MR000049 Acetaminophen Acetaminophen sulfate Conjugation - Sulfation SULT2A1 ... [10], [18], [19]
MR000050 Acetaminophen NAPQI Oxidation - Oxidation CYP2E1 ... [20], [21]
MR000047 NAPQI Acetaminophen cysteine Conjugation - Conjugation GSTM1 ... [10], [22], [18]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 102A1 (cyp102) DME1075 Bacillus megaterium
CPXB_BACMB
1.14.14.1
[2]
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[3]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[4]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[6]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[5]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[7]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[8]
Glutathione S-transferase alpha-1 (GSTA1) DME0011 Homo sapiens
GSTA1_HUMAN
2.5.1.18
[9]
Glutathione S-transferase mu-1 (GSTM1) DME0308 Homo sapiens
GSTM1_HUMAN
2.5.1.18
[10]
Glutathione S-transferase pi (GSTP1) DME0088 Homo sapiens
GSTP1_HUMAN
2.5.1.18
[10]
Glutathione S-transferase theta-1 (GSTT1) DME0093 Homo sapiens
GSTT1_HUMAN
2.5.1.18
[10]
Sulfotransferase 1A1 (SULT1A1) DME0008 Homo sapiens
ST1A1_HUMAN
2.8.2.1
[11]
Sulfotransferase 1A3 (SULT1A3) DME0063 Homo sapiens
ST1A3_HUMAN
2.8.2.1
[10]
Sulfotransferase 1A4 (SULT1A4) DMEN007 Homo sapiens
ST1A4_HUMAN
1.14.13.39
[12]
Sulfotransferase 2A1 (SULT2A1) DME0074 Homo sapiens
ST2A1_HUMAN
2.8.2.14
[10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[13]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DME0075 Homo sapiens
UD110_HUMAN
2.4.1.17
[10]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DME0072 Homo sapiens
UD16_HUMAN
2.4.1.17
[14]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[15]
UDP-glucuronosyltransferase 2B15 (UGT2B15) DME0049 Homo sapiens
UDB15_HUMAN
2.4.1.17
[16]
Unclear metabolic mechanism (DME-unclear) DME1265 Escherichia coli Not Available Not Available [17]
Unclear metabolic mechanism (DME-unclear) DME1396 Citrobacter freundii Not Available Not Available [17]
Unclear metabolic mechanism (DME-unclear) DME1398 Clostridioides difficile Not Available Not Available [17]
Unclear metabolic mechanism (DME-unclear) DME1418 Enterococcus faecalis Not Available Not Available [17]
⏷ Show the Full List of 26  DME(s)
References
1 Acetaminophen was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
3 Preferred orientations in the binding of 4'-hydroxyacetanilide (acetaminophen) to cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation studies. J Med Chem. 1994 Mar 18;37(6):860-7.
4 PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
5 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
6 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
7 Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
8 Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
9 Retinoid X receptor alpha regulates the expression of glutathione s-transferase genes and modulates acetaminophen-glutathione conjugation in mouse liver. Mol Pharmacol. 2005 Dec;68(6):1590-6.
10 Simultaneous quantification of abemaciclib and its active metabolites in human and mouse plasma by UHPLC-MS/MS J Pharm Biomed Anal. 2021 Sep 5;203:114225. doi: 10.1016/j.jpba.2021.114225.
11 Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008 Mar;82(3):155-65.
12 Metabolism and Effects on Endogenous Metabolism of Paracetamol (Acetaminophen) in a Porcine Model of Liver Failure. Metabolism and Effects on Endogenous Metabolism of Paracetamol (Acetaminophen) in a Porcine Model of Liver Failure
13 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
14 UGT1A6 and UGT2B15 polymorphisms and acetaminophen conjugation in response to a randomized, controlled diet of select fruits and vegetables. Drug Metab Dispos. 2011 Sep;39(9):1650-7.
15 Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
16 Characterization of niflumic acid as a selective inhibitor of human liver microsomal UDP-glucuronosyltransferase 1A9: application to the reaction phenotyping of acetaminophen glucuronidation. Drug Metab Dispos. 2011 Apr;39(4):644-52.
17 Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice. J Hepatol. 2018 Jul;69(1):51-59.
18 Application of a Volumetric Absorptive Microsampling (VAMS)-Based Method for the Determination of Paracetamol and Four of its Metabolites as a Tool for Pharmacokinetic Studies in Obese and Non-Obese Patients. Clin Pharmacokinet. 2022 Dec;61(12):1719-1733. doi: 10.1007/s40262-022-01187-2.
19 Evaluation of urinary acetaminophen metabolites and its association with the genetic polymorphisms of the metabolising enzymes, and serum acetaminophen concentrations in preterm neonates with patent ductus arteriosus. Xenobiotica. 2021 Nov;51(11):1335-1342. doi: 10.1080/00498254.2021.1982070.
20 Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents FASEB J. 2010 Dec;24(12):4904-16. doi: 10.1096/fj.10-162438.
21 Rapid detection and quantification of paracetamol and its major metabolites using surface enhanced Raman scattering. Analyst. 2023 Apr 11;148(8):1805-1814. doi: 10.1039/d3an00249g.
22 Detection of Distinct Distributions of Acetaminophen and Acetaminophen-Cysteine in Kidneys up to 10 m Resolution and Identification of a Novel Acetaminophen Metabolite Using an AP-MALDI Imaging Mass Microscope. J Am Soc Mass Spectrom. 2023 Jun 12. doi: 10.1021/jasms.3c00149.

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