Metabolism sulfate conjugates

Only the small amounts of T and T that are free in the circulation can be metabolized. The main route is deiodination of T to T and i-T, and from these to other inactive thyronines (21). Most of the Hberated iodide is reabsorbed in the kidney. Another route is the formation of glucuronide and sulfate conjugates at the 4 -OH in the Hver. These are then secreted in the bile and excreted in the feces as free phenols after hydrolysis in the lower gut. 

About 97% of po dose is absorbed from the GI tract. The dmg undergoes extensive first-pass hepatic metaboHsm and only 12% of the po dose is bioavailable. More than 95% is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.064—1.044 lg/mL. The dmg is metabolized in the Hver to 5-hyroxypropafenone, which has some antiarrhythmic activity, and to inactive hydroxymethoxy propafenone, glucuronides, and sulfate conjugates. Less than 1% of the po dose is excreted by the kidney unchanged. The elimination half-life is 2—12 h (32). 

Alternative pathways of activation of nitrosamines, including 3-hydroxylation followed by sulfate conjugation and the formation of alkoxydiazen-ium ions are discussed. The formation of alkyldiazo-nium ions from trialkyltriazenes is presented to show that the formation of the putative ultimate carcinogens from nitrosamines can be studied in a system not requiring metabolic activation,... 

Cerniglia CE, JP Freeman, RK Mitchum (1982b) Glucuronide and sulfate conjugation in the fungal metabolism of aromatic hydrocarbons. Appl Environ Microbiol 43 1070-1075. 

The concept of microbial models of mammalian metabolism was elaborated by Smith and Rosazza for just such a purpose (27-32). In principle, this concept recognizes the fact that microorganisms catalyze the same types of metabolic reactions as do mammals (32), and they accomplish these by using essentially the same type of enzymes (29). Useful biotransformation reactions common to microbial and mammalian systems include all of the known Phase I and Phase II metabolic reactions implied, including aromatic hydroxylation (accompanied by the NIH shift), N- and O-dealkylations, and glucuronide and sulfate conjugations of phenol to name but a few (27-34). All of these reactions have value in studies with the alkaloids. 

Many drugs and metabolites are metabolized by conjugation with sulfate or glucuronic acid as described in Chapter 7. Sulfate conjugates can be hydrolyzed back to the alcohol or phenol. Glucuronide conjugates can involve a wider variety of functional groups and... 

Moxifloxacin - Moxifloxacin is well absorbed from the Gl tract. The C ax attained 1 to 3 hours after oral dosing. Steady state is achieved after 3 days or more. Moxifloxacin is widely distributed throughout the body. Moxifloxacin is metabolized via glucuronide and sulfate conjugation. 

Sulfotransferases (SULTs) are important for the metabolism of a number of drugs, neurotransmitters, and hormones, especially the steroid hormones. The cosubstrate for these reactions is 3 -phosphoadenosine 5 -phosphosulfate (PAPS) (Fig. 4.1). Like the aforementioned enzymes, sulfate conjugation typically renders the compound inactive and more water soluble. However, this process can also result in the activation of certain compounds, such as the antihypertensive minoxidil and several of the steroid hormones. Seven SULT isoforms identified in humans, including SULTs lAl to 1A3, possess activity toward phenolic substrates such as dopamine, estradiol, and acetaminophen. SULTIBI possesses activity toward such endogenous substrates as dopamine and triiodothyronine. SULTIEI has substantial activity toward steroid hormones, especially estradiol and dehydroepiandrosterone, and toward the anti-... 

Propofol (Diprivan) is rapidly acting, has a short recovery time, and possesses antiemetic properties. A rapid onset of anesthesia (50 seconds) is achieved, and if no other drug is administered, recovery will take place in 4 to 8 minutes. The recovery is attributed to redistribution of the drug and rapid metabolism to glucuronide and sulfate conjugates by the liver and extrahepatic tissues, such as intestine and kidney. 

Curcumin (diferuloylmethane) has very low oral bioavailability, but is rapidly absorbed and low nanomolar levels of the parent compound and its glucuronide and sulfate conjugates can be detected in human plasma and portal circulation after very high (nondietary) intakes (3.6g/day for 1 week). Metabolic reduction occurs in the liver, and glutathione adducts have been observed in vitro ... 

It is metabolized in liver to glucuronic acid and sulfate conjugates and excreted in urine. 

After oral administration, it is completely absorbed and is concentrated in lepromatous skin, liver, kidney and muscles. It is metabolized in liver and excreted in urine as glucuronic acid and sulfate conjugates. 

The major pathway of coumarin metabolism in most human subjects is 7-hydroxyl-ation to form 7-hydroxy coumarin, which is excreted in the urine as both glucuronic acid and sulfate conjugates. Coumarin 7-hydroxylation activity exhibits a Gaussian distribution in Caucasian populations (Cholerton et al, 1992 Rautio et al, 1992), but some individuals are deficient in this activity. 

Apart from glucuronic acid and sulfate conjugation of hydroxycoumarins, other phase II pathways of coumarin metabolism have been identified. For example, ortho-coumaric acid may be conjugated with glycine (Lake, 1999), and a coumarin mercapturic acid conjugate has also been reported (Huwer et al., 1991). Coumarin may also be metabolized by the gastrointestinal microflora to 3,4-dihydrocoumarin and ort/io-hydroxyphenylpropionic acid under anaerobic conditions (Scheline, 1968). 

Concerning HBAs, their metabolism involves conjugation with sulfate, glucuronate and glycine. Methylation may also occur, as may demethylation, dehydroxylation and decarboxylation (this only if there is a 4-hydroxyl) [3],... 

The absorption of spectinomycin is poor via the oral route, but rapid and extensive after intramuscular injection. It is not extensively metabolized in animals and rapidly excreted in the urine (16). Following subcutaneous injections of spectinomycin sulfate to cattle, 70-83% of the dose was excreted in the urine and 62-64% of this was parent spectinomycin (17). Several minor metabolites were found in the urine that consisted mostly of dihydroxyspectinomycin and two acetylated isomers, and an unusual ammoniated spectinomycin metabolite and its acetylated derivative. There was also some evidence, but it was not compelling, for a spectinomycin sulfate conjugate. Dihydrospectinomycin and parent spectinomycin were the only identifiable major components found in the liver and the kidney, respectively. Liver and kidney retained the highest concentrations of total residues throughout the 15-day withdrawal period. 

In sheep orally dosed with 40 mg/kg bw radiolabeled thiophanate, only the parent drug and its major metabolite lobendazole could be detected in plasma for 65 h after dosing. In sheep liver, thiophanate was metabolized to lobendazole at a rate of approximately 34%. Other metabolites included 2-aminobenzimidaz-ole, low molecular-weight aliphatic acids, and limited amounts of the glucuronide and sulfate conjugates. 

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