Disease relevance of Acetaminophen glucuronide

• The rats with renal failure converted most of the administered dose to acetaminophen sulfate, whereas normal animals metabolized much of the drug to acetaminophen glucuronide [1].
• Acute cholestasis increased the total clearance of acetaminophen 20%, the partial clearance to acetaminophen sulfate 12%, and the partial clearance to acetaminophen glucuronide 85% [2].

Psychiatry related information on Acetaminophen glucuronide

• However, after at least 24 hr of food deprivation, hepatic UDP-glucuronic acid and acetaminophen-glucuronide concentrations were significantly depressed by ethanol [3].

High impact information on Acetaminophen glucuronide

• Formation of the acetaminophen glucuronide conjugate measured by high-performance liquid chromatography was quantified by the ratio of the area under the plasma concentration-time curve (AUC) from 0 to 2 hours for the acetaminophen glucuronide divided by the AUC for acetaminophen [4].
• The contributions of hepatic glycogenolysis to fasting glucose production and direct pathway to hepatic glycogen synthesis were quantified in eight type 1 diabetic patients and nine healthy control subjects by ingestion of (2)H(2)O and acetaminophen before breakfast followed by analysis of urinary water and acetaminophen glucuronide [5].
• Fluxes were calculated using tracer dilution techniques and mass isotopomer distribution analysis in plasma glucose and urinary paracetamol-glucuronide after infusion of [U-(13)C]glucose, [2-(13)C]glycerol, [1-(2)H]galactose, and paracetamol [6].
• The rate of metabolism of acetaminophen by hepatocytes was much slower in 2H2O buffer compared to H2O buffer and selective deuteration of several metabolites including the ketone bodies, glucose, and acetaminophen glucuronide was observed [7].
• Hemodialysis was the major or sole routine of elimination of acetaminophen glucuronide and sulfate in the anephric patients [8].

Biological context of Acetaminophen glucuronide

• The pharmacokinetics of acetaminophen and the two major processes specifically responsible for its elimination, namely, the formations of acetaminophen sulfate and acetaminophen glucuronide, were used to assess hepatic conjugating activity [2].
• To determine the functional impact of up-regulation of Mrp3 versus Mrp2, we measured the excretion of acetaminophen glucuronide (APAP-glu), a common substrate for both transporters, into bile and perfusate in the recirculating isolated perfused liver (IPL) model [9].
• The metabolic ratios unchanged acetaminophen/acetaminophen glucuronide in UGT1A1-wildtypes, heterozygotes and mutants showed no statistically significant differences [10].
• Pharmacokinetic study of the enterohepatic circulation of acetaminophen glucuronide in rats [11].
• To assess whether acetaminophen glucuronide accurately reflects uridyl diphosphate-glucose (UDP-glucose) derived from gluconeogenesis during fasting, three mongrel dogs received infusions of [U-14C]lactate, [1-13C]galactose, and [6-3H]glucose (after fasting overnight or for 2.5 days) [12].

Anatomical context of Acetaminophen glucuronide

• Formation rates of acetaminophen-O-glucuronide (APAPG), morphine-3-glucuronide (M3G), and oestradiol-3-glucuronide (E3G) as probes for UGT1A6, 2B7, and 1A1, respectively, were determined in human kidney, liver, and lung microsomes, and in microsomes from intestinal mucosa corresponding to duodenum, jejunum and ileum [13].
• AG was detected only in cytosol [14].
• High-performance liquid chromatographic assay for acetaminophen glucuronide in human liver microsomes [15].
• The plasma concentrations and the resultant AUC0-12 h of acetaminophen, acetaminophen-glucuronide, and acetaminophen-sulfate were significantly higher when blood samples were collected from the retro-orbital sinus than those from the jugular vein [16].

Associations of Acetaminophen glucuronide with other chemical compounds

• Acetaminophen and its two major metabolites, acetaminophen glucuronide and acetaminophen sulfate in plasma and urine, were determined by a sensitive and specific high-performance liquid chromatography assay [17].
• Phenobarbital pretreatment did not alter significantly the unbound fractions of acetaminophen, AG or AS in hepatic cytosol [14].
• The effect of probenecid (PRB) on factors regulating the hepatic disposition of acetaminophen glucuronide (AG) was investigated in vitro [18].
• The aim of this study was to compare the pharmacokinetics of paracetamol (PCM) and its metabolites [paracetamol glucuronide (PCM-G), paracetamol sulfate (PCM-S), and paracetamol cysteine (PCM-C)] in 16 patients with 16 normal subjects [19].

Gene context of Acetaminophen glucuronide

• Studies in knockout mice have shown that Mrp3 contributes to the transport of morphine-3-glucuronide and acetaminophen-glucuronide from the liver into blood [20].
• Altered hepatobiliary disposition of acetaminophen glucuronide in isolated perfused livers from multidrug resistance-associated protein 2-deficient TR(-) rats [21].
• No significant differences were noted in either ClR or CLf of AG and AS in female CF mice [22].
• CLR of AG was 6.3 and 4.8 mL/min per kg and CLf of AG was 9.6 and 8.9 mL/min per kg for homozygous and heterozygous males, respectively, although not reaching statistical significance [22].
• This method is suitable for in vitro studies using acetaminophen glucuronide formation as an index reaction for UGT activity [15].

Analytical, diagnostic and therapeutic context of Acetaminophen glucuronide

• However, renal ligation did not alter the percentage of the dose excreted as AG in bile despite a marked elevation in AG serum concentrations [23].
• The absolute amounts and ratio of paracetamol glucuronide to sulphate, the major urinary metabolites after therapeutic paracetamol doses, were similar after jejunal administration as compared to oral administration [24].
• A strong positive correlation was found between the renal clearances of acetaminophen glucuronide and acetaminophen sulfate, possibly due to blood perfusion rate-dependent renal tubular secretion of the two conjugates [25].
• A capillary electrophoresis (CE) method was developed using paracetamol glucuronide as a novel probe for human beta-glucuronidase activity [26].

References