Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Acetaminophen biotransformation

Yu D, Renedo OD, Blankert B, Sima V, Sandulescu R, Arcos J, Kauffmann J-M (2006) A peroxidase-based biosensor supported by nanoporous magnetic silica microparticles for acetaminophen biotransformation and inhibition studies. Electroanalysis 18 1637-1642... [Pg.261]

The most important removal pathways of PhACs during wastewater treatment are biotransformation/biodegradation and abiotic removal by adsorption to the sludge. The efficiency of their removal at WWTP depends on their physico-chemical properties, especially hydrophobicity and biodegradability, and process operating parameters (i.e., HRT, SRT, and temperature). For certain NSAIDs (e.g., ibuprofen, acetaminophen), high removals (>90%) are consistently reported in literature... [Pg.204]

As an example, acetaminophen (APAP) in overdose has been used by several groups to identify hepatotoxicity biomarkers in mice. APAP-induced hepatotoxicity is characterized by hepatic centrilobular necrosis and hepatitis. APAP biotransformation by Phase I enzymes leads to the formation of the reactive metabolite N-acetyl-p-benzoquinone (NAPQI), which can deplete glutathione and form adducts with hepatic proteins (see Section 15.2). Protein adduction primes the hepatocytes for cytokines released by activated macrophages (Kupffer cells) and/or destructive insults by reactive nitrogen species. Although necrosis is recognized as the mode of cell death in APAP overdose, the precise mechanisms are still being elucidated [152]. [Pg.373]

While the term biotransformation generally implies inactivation and detoxification, there are exceptional cases where a metabolite is more chemically active or more toxic than the parent compound. In these situations, the processes of bioactivation and biotoxification are said to have occurred, respectively. An example of bioactivation is the formation of the commonly used drug acetaminophen from phenacetin in the liver (see Figure 3.2). The latter drug was once widely used as an analgesic agent but because of kidney toxicity has been replaced by other more potent, less toxic substitutes including, of course, acetaminophen itself. In this particular bioactivation pathway the process occurs via normal oxidative dealkylation. [Pg.48]

The mechanism of acute acetaminophen nephrotoxicity is related to the bioactivation of acetaminophen and/or its metabolites to highly reactive species which are capable of arylating renal macromolecules or generating reactive oxygen species. Acetaminophen hepatotoxicity is the result of conversion of acetaminophen to the reactive intermediate N-acetyl-p-benzoquinoneimine (NAPQI), which can covalently bind to hepatic macromolecules. It is less clear what role formation of NAPQI in the kidney plays in acetaminophen nephrotoxicity. In some species (e.g., the Fischer 344 rat) deacetylation appears to be an important biotransformation step in acetaminophen nephrotoxicity, while in other species (e.g., the CD-I mouse), bioactivation does not appear to require deacetylation of acetaminophen before the ultimate nephrotoxicant species is produced. Therefore, the role of NAPQI in acute acetaminophen nephrotoxicity might be species dependent. [Pg.1486]

Biotransformation of acetaminophen by deace-tylase enzymes in liver or kidney produces the metabolite 4-aminophenol (Figure 4). Evidence suggests that acetaminophen nephrotoxicity may result from 4-aminophenol formation. In animal studies, 4-ami-nophenol is a more potent nephrotoxicant than acetaminophen and inhibition of deacetylase enzymes also attenuates acetaminophen nephrotoxicity. Deacetylase enzymes are also present in higher levels in renal cortex, the target for acetaminophen nephrotoxicity, than in liver or renal medulla and there is a positive correlation between renal cortex... [Pg.1486]

See also Acetaminophen Acetylaminofluorene Acetyl-salicylic Acid Aflatoxin Biotransformation Blood Bromo-benzene Carbon Tetrachloride Chloroform Dioxins Distribution Ethanol Excretion Immune System Is-oniazid Lipid Peroxidation Metallothionein Peroxisome Proliferators Tissue Repair. [Pg.1554]

Novel Biotransformation Pathways - The recent literature contains examples of some of the newly discovered pathways in addition to those covered in the excellent review by Jenner and Testa.Formation of an aliphatic 0-methyl metabolite (26) of the antiinflammatory agent cicloprofen (27) in the rat, has been demonstrated,and it was proposed that it formed via 0-raethylation of a dihydroxy intermediate (28). Thiomethyl metabolites of phenacetin and acetaminophen have been found in dogs and man. An S-methyl metabolite (29) of bromazepam (50), a minor tranquilizer, in the rat was shown to be formed vitro by biotransformation of a mecapturic acid conjugate (31). [Pg.194]

The biotransformation of paracetamol (acetaminophen) at therapeutic concentrations in man can be seen in Figure 1. The major route of metabolism is via conjugation of the phenolic -OH group. The hepatic sulphotransferases have a high affinity for paracetamol (acetaminophen) but are rapidly saturated (either due to cofactor depletion or limited sulphotransferase availability), as were the uridine diphosphate glucuronosyl transferases (UDPGTs) which... [Pg.255]


See other pages where Acetaminophen biotransformation is mentioned: [Pg.268]    [Pg.891]    [Pg.275]    [Pg.276]    [Pg.220]    [Pg.266]    [Pg.267]    [Pg.499]    [Pg.16]    [Pg.274]    [Pg.540]    [Pg.837]    [Pg.69]    [Pg.731]    [Pg.225]    [Pg.721]    [Pg.891]    [Pg.562]    [Pg.145]    [Pg.98]    [Pg.1257]    [Pg.1715]    [Pg.1869]    [Pg.2134]    [Pg.16]    [Pg.109]    [Pg.266]    [Pg.267]    [Pg.193]    [Pg.685]    [Pg.686]    [Pg.264]    [Pg.467]    [Pg.1117]    [Pg.553]    [Pg.553]    [Pg.165]    [Pg.168]    [Pg.447]    [Pg.685]    [Pg.3]   
See also in sourсe #XX -- [ Pg.36 ]

See also in sourсe #XX -- [ Pg.562 ]




SEARCH



© 2024 chempedia.info