Page last updated: 2024-12-07

acetaminophen glucuronide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Acetaminophen glucuronide is a major metabolite of acetaminophen (paracetamol), a widely used analgesic and antipyretic drug. It is formed in the liver by the enzyme UDP-glucuronosyltransferases (UGTs). Acetaminophen glucuronide is a water-soluble compound and is readily excreted in the urine. It is considered to be a pharmacologically inactive metabolite of acetaminophen. Studies on acetaminophen glucuronide have focused on its role in acetaminophen metabolism and excretion, as well as its potential contribution to the hepatotoxicity of acetaminophen. Acetaminophen glucuronide is an important marker of acetaminophen metabolism and can be used to assess the effectiveness of acetaminophen treatment. It is studied to better understand the pharmacokinetics of acetaminophen, to evaluate the efficacy and safety of acetaminophen treatment, and to develop strategies to reduce the risk of acetaminophen hepatotoxicity.'

acetaminophen glucuronide: acetaminophen metabolite in rats [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

acetaminophen O-beta-D-glucosiduronic acid : A beta-D-glucosiduronic acid that is the O-glucuronide of paracetamol (acetaminophen). [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID83944
CHEMBL ID1647
CHEBI ID32636
SCHEMBL ID935911
MeSH IDM0113195

Synonyms (32)

Synonym
acetaminophen o-beta-d-glucosiduronic acid
16110-10-4
CHEBI:32636 ,
paracetamol glucuronide
acetaminophen glucuronide
4-acetamidophenyl beta-d-glucopyranosiduronic acid
beta-d-glucopyranosiduronic acid, 4-(acetylamino)phenyl
4-acetamidophenol glucuronide
CHEMBL1647
(2s,3s,4s,5r,6s)-6-(4-acetamidophenoxy)-3,4,5-trihydroxyoxane-2-carboxylic acid
unii-8be7g9r76x
8be7g9r76x ,
.beta.-d-glucopyranosiduronic acid, 4-(acetylamino)phenyl
4-glucuronosidoacetanilide
SCHEMBL935911
W-201461
acetaminophen d-glucuronide
AKOS030211071
paracetamol beta-d-glucuronide, analytical standard
4-acetamidophenyl b-d-glucopyranosiduronic acid
4-acetamidophenyl beta-delta-glucopyranosiduronic acid
4-(acetylamino)phenyl beta-d-glucopyranosiduronic acid
4-(acetylamino)phenyl beta-delta-glucopyranosiduronic acid
4-acetamidophenyl b-delta-glucopyranosiduronic acid
p-acetamidophenyl beta-d-glucuronide
acetaminophen beta-d-glucuronide, min. 95%
sodium (2s,3s,4s,5r,6s)-6-(4-acetamidophenoxy)-3,4,5-trihydroxy-tetrahydropyran-2-carboxylate
DTXSID30936449
Q27115028
(2s,3s,4s,5r,6s)-6-(4-acetamidophenoxy)-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
HY-113083
CS-0059518

Research Excerpts

Toxicity

ExcerptReferenceRelevance
"Acetaminophen is eliminated primarily by glucuronidation, thereby avoiding cytochrome P450-catalyzed bioactivation to a toxic reactive intermediate."( Biotransformation and toxicity of acetaminophen in congenic RHA rats with or without a hereditary deficiency in bilirubin UDP-glucuronosyltransferase.
Chow, SY; de Morais, SM; Wells, PG, 1992
)
0.28
" One of the mechanisms for this protection appears to be the decreased AA toxic activation via P-450, as well as increased detoxication via glucuronidation of AA."( Protective effects of fulvotomentosides on acetaminophen-induced hepatotoxicity.
Jia, XS; Klaassen, CD; Liu, J; Liu, YP; Madhu, C; Mao, Q, 1992
)
0.28
"We investigated the effect of aging on hepatic pharmacokinetics and the degree of hepatotoxicity following a toxic dose of acetaminophen."( The effect of aging on acetaminophen pharmacokinetics, toxicity and Nrf2 in Fischer 344 rats.
Cogger, VC; de Cabo, R; Hilmer, SN; Huizer-Pajkos, A; Jones, BE; Le Couteur, DG; Mach, J; McKenzie, C, 2014
)
0.4

Pharmacokinetics

The present study was to investigate the effects of giving N-acetylcysteine (NAC) alone and in combination with either glycyrrhizin (GL), silibinin (SIB) or spironolactone. A pharmacokinetic model of the enterohepatic circulation of acetaminophen glucuronide was investigated in rats.

ExcerptReferenceRelevance
" The pharmacokinetic results obtained with microdialysis sampling were the same as those obtained from blood collection."( In vivo microdialysis sampling for pharmacokinetic investigations.
Lunte, CE; Puckett, DL; Scott, DO; Sorenson, LR; Steele, KL, 1991
)
0.28
"A pharmacokinetic model of the enterohepatic circulation of acetaminophen glucuronide was investigated in rats with particular attention to a lag time between biliary excretion and reabsorption."( Pharmacokinetic study of the enterohepatic circulation of acetaminophen glucuronide in rats.
Hanawa, M; Iwai, M; Kaneniwa, N; Watari, N, 1984
)
0.75
"Successful pharmacokinetic modeling often requires the ability of a simple model to describe a complex series of physiological processes."( Hepatic disposition of acetaminophen and metabolites. Pharmacokinetic modeling, protein binding and subcellular distribution.
Brouwer, KL; Studenberg, SD, 1993
)
0.29
" However, a significantly shorter elimination half-life of PCM was observed in the thalassemic subjects (p<0."( A pharmacokinetic study of paracetamol in Thai beta-thalassemia/HbE patients.
Chantharaksri, U; Fucharoen, P; Fucharoen, S; Howard, TA; Morales, NP; Sanvarinda, Y; Sirankapracha, P; Tankanitlert, J; Temsakulphong, A; Ware, RE, 2006
)
0.33
" Our pharmacokinetic data provide additional evidence that plasma PCM-G is higher in thalassemic patients with hyperbilirubinemia, which could be a casual relationship in regulating the UDP-glucuronosyltransferase expression."( A pharmacokinetic study of paracetamol in Thai beta-thalassemia/HbE patients.
Chantharaksri, U; Fucharoen, P; Fucharoen, S; Howard, TA; Morales, NP; Sanvarinda, Y; Sirankapracha, P; Tankanitlert, J; Temsakulphong, A; Ware, RE, 2006
)
0.33
" Paracetamol clearance showed a statistically significant dependence on age group, whereas volume of distribution during elimination and elimination half-life were associated with age group and sex, respectively."( Pharmacokinetics of intravenous paracetamol in elderly patients.
Aantaa, R; Kuusniemi, K; Liukas, A; Neuvonen, PJ; Niemi, M; Olkkola, KT; Virolainen, P, 2011
)
0.37
" The pharmacokinetic changes described may decrease susceptibility to acetaminophen-induced hepatotoxicity but may increase risk of nephrotoxicity in old age."( The effect of aging on acetaminophen pharmacokinetics, toxicity and Nrf2 in Fischer 344 rats.
Cogger, VC; de Cabo, R; Hilmer, SN; Huizer-Pajkos, A; Jones, BE; Le Couteur, DG; Mach, J; McKenzie, C, 2014
)
0.4
" The present study was to investigate the effects of giving N-acetylcysteine (NAC) alone and in combination with either glycyrrhizin (GL), silibinin (SIB) or spironolactone (SL) on the plasma pharmacokinetic (PK) profiles, hepatic exposure, biliary excretion and urinary excretion of acetaminophen (APAP) and its major metabolite, acetaminophen glucuronide (AG)."( Changes in pharmacokinetic profiles of acetaminophen and its glucuronide after pretreatment with combinations of N-acetylcysteine and either glycyrrhizin, silibinin or spironolactone in rat.
Liu, X; Wang, Q; Xu, R; Yang, J; Zang, M; Zhang, J, 2014
)
0.57
" The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo."( Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen.
Court, MH; Epstein, CR; Giesing, D; Greenblatt, DJ; Harmatz, JS; Kadota, T; Kurosaki, C; Nakagawa, Y; Nakamura, T; Zhao, Y, 2015
)
0.42
" In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed."( Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen.
Court, MH; Epstein, CR; Giesing, D; Greenblatt, DJ; Harmatz, JS; Kadota, T; Kurosaki, C; Nakagawa, Y; Nakamura, T; Zhao, Y, 2015
)
0.42
"The pharmacokinetic (PK) profile of a drug is influenced by several factors, which can lead to a suboptimal dosing regimen in specific patient populations."( 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.
Boffel, L; De Baerdemaeker, L; Delahaye, L; Stove, CP, 2022
)
0.72

Bioavailability

ExcerptReferenceRelevance
"1 The rate of absorption of oral paracetamol depends on the rate of gastric emptying and is usually rapid and complete."( Kinetics and metabolism of paracetamol and phenacetin.
Prescott, LF, 1980
)
0.26

Dosage Studied

ExcerptRelevanceReference
"03) at 4 hr after dosing following SURc 800."( Plasma concentration of paracetamol and its major metabolites after p.o. dosing with paracetamol or concurrent administration of paracetamol and its N-acetyl-DL-methionine ester in mice.
Ingebrigtsen, K; Lausund, P; Nafstad, I; Skoglund, LA, 1992
)
0.28
" Rabbits were dosed intravenously with acetaminophen (NAPA, 30 mg/kg)."( A method for the preparation of calibration curves for acetaminophen glucuronide and acetaminophen sulfate in rabbit urine without use of authentic compounds in high-performance liquid chromatography.
Baba, S; Nakamura, J; Nakamura, T; Sasaki, H; Shibasaki, J, 1987
)
0.52
" Bile was collected prior to dosing and for 5-6 hours after dosing at varying time intervals."( BHA (2(3)-tert-butyl-4-hydroxyanisole)-mediated modulation of acetaminophen phase II metabolism in vivo in Fisher 344 rats.
Boroujerdi, M; McLaughlin, WJ, 1987
)
0.27
" Biliary excretion of the various metabolites of acetaminophen increased from 20 to 49% as the dosage was increased from 37."( Glucuronidation and biliary excretion of acetaminophen in rats.
Hjelle, JJ; Klaassen, CD, 1984
)
0.27
" It is not clear why regular dosing with paracetamol in haemodialysis patients did not cause the accumulation of paracetamol glucuronide or sulphate as predicted."( The disposition of paracetamol and its conjugates during multiple dosing in patients with end-stage renal failure maintained on haemodialysis.
Martin, U; Prescott, LF; Temple, RM; Winney, RJ, 1993
)
0.29
" Combined UV, 1H NMR, and positive-ion electrospray MS detection was achieved in the continuous-flow mode using whole human urine from a subject dosed with acetaminophen."( Combined HPLC, NMR spectroscopy, and ion-trap mass spectrometry with application to the detection and characterization of xenobiotic and endogenous metabolites in human urine.
Foxall, PJ; Lindon, JC; Nicholson, JK; Shockcor, JP; Unger, SE; Wilson, ID, 1996
)
0.29
" Male Sprague-Dawley rats were each dosed with either phenacetin or phenacetin-C2H3 at 50 mg kg-1."( NMR spectroscopic studies on the metabolism and futile deacetylation of phenacetin in the rat.
Caddick, S; Farrant, RD; Lindon, JC; Nicholls, AW; Nicholson, JK; Wilson, ID, 1997
)
0.3
"To investigate the pharmacokinetics, metabolism, and dose-response relation of a single rectal dose of paracetamol in preterm infants in two different age groups."( Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates.
Anand, KJ; Deinum, JT; Kuizenga, AJ; Okken, A; Quak, JM; Tibboel, D; van Dam, JG; van Lingen, RA, 1999
)
0.3
"5, 2, 3, 4, 5, 7, and 9 h after dosing for determination of the plasma levels of PCM and its metabolites by high-performance liquid chromatography."( A pharmacokinetic study of paracetamol in Thai beta-thalassemia/HbE patients.
Chantharaksri, U; Fucharoen, P; Fucharoen, S; Howard, TA; Morales, NP; Sanvarinda, Y; Sirankapracha, P; Tankanitlert, J; Temsakulphong, A; Ware, RE, 2006
)
0.33
" The value for area under the concentration-time curve over the 6h dosing interval of venous plasma (45."( Investigating paracetamol pharmacokinetics using venous and capillary blood and saliva sampling.
McLachlan, AJ; Rittau, AM, 2012
)
0.38
" This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach."( Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants.
Allegaert, K; Danhof, M; de Hoon, J; Knibbe, CA; Krekels, EH; Tibboel, D; van Ham, S, 2015
)
0.42
"Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion."( Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood.
Azuine, RE; Hong, X; Hou, W; Ji, Y; Pearson, C; Riley, A; Wang, G; Wang, X; Zhang, Y; Zuckerman, B, 2020
)
0.56
"The pharmacokinetic (PK) profile of a drug is influenced by several factors, which can lead to a suboptimal dosing regimen in specific patient populations."( 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.
Boffel, L; De Baerdemaeker, L; Delahaye, L; Stove, CP, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
drug metabolitenull
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
beta-D-glucosiduronic acidA glucosiduronic acid resulting from the formal condensation of any substance with beta-D-glucuronic acid to form a glycosidic bond.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (1)

PathwayProteinsCompounds
Acetaminophen Metabolism Pathway3016

Bioassays (5)

Assay IDTitleYearJournalArticle
AID679313TP_TRANSPORTER: In vivo biliary excretion in vivo, biliary excretion of Wistar/TR- rat2003Drug metabolism and disposition: the biological fate of chemicals, Jun, Volume: 31, Issue:6
Hepatobiliary excretion of acetaminophen glutathione conjugate and its derivatives in transport-deficient (TR-) hyperbilirubinemic rats.
AID679812TP_TRANSPORTER: decrease in biliary excretion in isolated perfused liver from TR- rat2000The Journal of pharmacology and experimental therapeutics, Nov, Volume: 295, Issue:2
Altered hepatobiliary disposition of acetaminophen glucuronide in isolated perfused livers from multidrug resistance-associated protein 2-deficient TR(-) rats.
AID404304Effect on human MRP2-mediated estradiol-17-beta-glucuronide transport in Sf9 cells inverted membrane vesicles relative to control2008Journal of medicinal chemistry, Jun-12, Volume: 51, Issue:11
Prediction and identification of drug interactions with the human ATP-binding cassette transporter multidrug-resistance associated protein 2 (MRP2; ABCC2).
AID680201TP_TRANSPORTER: inhibition of E1S uptake (E1S: 0.05 uM, Acetaminophen glucuronide: 500 uM) in Xenopus laevis oocytes2000The Journal of biological chemistry, Feb-11, Volume: 275, Issue:6
Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.
AID1292832Renal clearance in healthy human assessed as paracetamol glucuronide level at 20 mg/kg1980British journal of clinical pharmacology, Oct, Volume: 10 Suppl 2Kinetics and metabolism of paracetamol and phenacetin.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (136)

TimeframeStudies, This Drug (%)All Drugs %
pre-199029 (21.32)18.7374
1990's32 (23.53)18.2507
2000's42 (30.88)29.6817
2010's28 (20.59)24.3611
2020's5 (3.68)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 26.68

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index26.68 (24.57)
Research Supply Index5.05 (2.92)
Research Growth Index4.54 (4.65)
Search Engine Demand Index34.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (26.68)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials13 (9.15%)5.53%
Reviews1 (0.70%)6.00%
Case Studies2 (1.41%)4.05%
Observational1 (0.70%)0.25%
Other125 (88.03%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]