16110-10-4

Usage

Uses

Used in Pharmaceutical Industry:
Acetaminophen glucuronide is used as a metabolite in the pharmaceutical industry for the development and evaluation of paracetamol (acetaminophen) as a pain reliever and fever reducer. Its presence in the body can be used to monitor the metabolism and efficacy of paracetamol, as well as to assess potential drug interactions and side effects.
Used in Clinical Research:
Acetaminophen glucuronide is used as a biomarker in clinical research for studying the pharmacokinetics and pharmacodynamics of paracetamol. It helps researchers understand how the drug is processed in the body, its distribution, and its elimination, which can be crucial for optimizing dosages and minimizing adverse effects.
Used in Drug Metabolism Studies:
Acetaminophen glucuronide is used as a research tool in drug metabolism studies to investigate the role of glucuronidation in the metabolism of various drugs. This can provide insights into the mechanisms of drug detoxification and the potential for drug-drug interactions, leading to the development of safer and more effective medications.
Used in Toxicology:
Acetaminophen glucuronide is used in toxicology to assess the risk of acetaminophen-induced liver damage. High levels of paracetamol can lead to the formation of a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which can cause liver injury. Monitoring the levels of acetaminophen glucuronide can help determine the extent of paracetamol metabolism and the potential for liver toxicity.

InChI:InChI=1/C14H17NO8/c1-6(16)15-7-2-4-8(5-3-7)22-14-11(19)9(17)10(18)12(23-14)13(20)21/h2-5,9-12,14,17-19H,1H3,(H,15,16)(H,20,21)/t9-,10-,11+,12-,14+/m0/s1

Upstream product

• 103-90-2 4-acetaminophenol 
• 2616-64-0 UDP-glucuronic acid 
• 78132-48-6 uridine-diphosphate-glucuronic acid triammonium salt 
• 30824-21-6 methyl <4-(acetamido)phenyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid>uronate 
• 92420-89-8 methyl 2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-α-D-glucopyranuronate 
• 72692-06-9 methyl 2,3,4-tri-O-acetyl-D-glucopyranuronate 
• 21080-66-0 O¹-(4-amino-phenyl)-β-D-glucopyranuronic acid 
• 108-24-7 acetic anhydride 

Downstream Products

• 30824-21-6 methyl <4-(acetamido)phenyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid>uronate 

Relevant academic research and scientific papers

Preparation and characterisation of solid state forms of paracetamol-O-glucuronide

The synthesis and crystallisation of the pharmaceutically important metabolite, paracetamol-O-glucuronide, is described. Hydrated and anhydrous forms of the target molecule have been characterised by PXRD, DSC and TGA. In addition, a methanol solvate has

Glucuronidation of paracetamol by human liver microsomes in vitro: Enzyme kinetic parameters and interactions with short-chain aliphatic alcohols and opiates

In this study, glucuronidation of paracetamol (CAS 103-90-2) by human liver microsomes and the effects of aliphatic alcohols and opiates were investigated. Paracetamol glucuronidation was optimised for various incubation conditions. Ten different aliphatic alcohols and the opiates morphine, codeine and dihydrocodeine were analysed as inhibitors of paracetamol glucuronidation. Furthermore, the effects of paracetamol on morphine-3 and codeine glucuronidation were investigated. Enzyme kinetic analysis was carried out via determination of the parameters Km, Vmax, Ki and the type of inhibition. Except for methanol and ethanol, all investigated alcohols inhibited glucuronidation of paracetamol. Ki values ranged between 4.59 mmol/l (n-pentanol) and 340.54 mmol/l (2-propanol). Extent of inhibition strongly depended on the structure and clearly increased with the length of the alkyl chain. All tested opiates inhibited paracetamol glucuronidation with Ki values between 4.02 mmol/l (dihydrocodeine) and 11.44 mmol/l (morphine). Paracetamol itself turned out to be an inhibitor of opiate glucuronidation. The apparent Ki values were 4.62 mmol/l (inhibition of morphine-3 glucuronidation) and 9.44 mmol/l (inhibition of codeine glucuronidation). A mixed inhibition type was determined for all substances. The in vitro studies show a great inhibition potential for the analysed substances. Transferring the results to the in vivo situation, a higher liver toxicity of paracetamol can be assumed, if concomitantly a lot of alcoholic beverages with congener alcohols - e.g. fruit schnapps or whisky - are drunk or if opiates - as analgesics or narcotics - are taken in higher doses. ECV Editio Cantor Verlag.

Glucuronidation in the chimpanzee (Pan troglodytes): Studies with acetaminophen, oestradiol and morphine

The chimpanzee has recently been characterized as a surrogate for oxidative drug metabolism in humans and as a pharmacokinetic model for the selection of drug candidates. In the current study, the glucuronidation of acetaminophen, morphine and oestradiol was evaluated in the chimpanzee to extend the characterization of this important animal model. Following oral administration of acetaminophen (600 mg) to chimpanzees (n = 2), pharmacokinetics were comparable with previously reported human values, namely mean oral clearance 0.91 vs. 0.62 ± 0.05 l h-1 kg-1, apparent volume of distribution 2.29 vs. 1.65 ± 0.25 l kg-1, and half-life 1.86 vs. 1.89 ± 0.27 h, for chimpanzee vs. human, respectively. Urinary excretions (percentage of dose) of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate were also similar between chimpanzees and humans, namely 2.3 vs. 5.0, 63.1 vs. 54.7, and 25.0 vs. 32.3%, respectively. Acetaminophen, oestradiol and morphine glucuronide formation kinetics were investigated using chimpanzee (n = 2) and pooled human liver microsomes (n = 10). V maxapp and Kmapp (or S 50app) for acetaminophen glucuronide, morphine 3- and 6-glucuronide, and oestradiol 3- and 17-glucuronide formation were comparable in both species. Eadie-Hofstee plots of oestradiol 3-glucuronide formation in chimpanzee microsomes were characteristic of autoactivation kinetics. Western immunoblot analysis of chimpanzee liver microsomes revealed a single immunoreactive band when probed with anti-human UGT1A1, anti-human UGT1A6, and anti-human UGT2B7. Taken collectively, these data demonstrate similar glucuronidation characteristics in chimpanzees and humans.