Metabolic product, label

An interesting set of central nervous system properties has also been discovered and studied (Table VI-10). The work devoted to piscaine must be emphasized besides finding hypnotic properties of 2-amino-4-phenyl-thiazole on fish, the authors studied the structure of the metabolite, as well as the localization of the (radio labeled) metabolic product in various organs. Recently, thiazol-4-yl methoxyamine was shown to inhibit the development of morphine tolerance (1607). 5-Aminothiazole derivatives such as 419a were proposed as cardiovascular agents (1608, 1610). Substitution of the 5-aminothiazole radical on the cephalophosphorin structure gives a series of antibacterial products (1609). 

Figure 2.17 Application of the reverse DEPT pulse sequence to monitor C-labeled glucose by mouse liver-cell extract. (A) Normal FT spectrum. (B) Reverse DEPT spectrum showing the a- and )3-anomeric proton resonances. (C) Two different CH2 proton resonances, a and b, appear after 1.5 h of metabolism. (D) Edited H spectrum confirming that the CH2 resonances arise from metabolic products. (Reprinted from J. Magn. Resonance 56, Brooks et al., 521, copyright 1984, Academic Press.)...

Addison RF, Willis DE (1978) The metabolism by rainbow trout (salvo garidnerri) of p,p-[14C]DDT and some of its possible degradation products labeled with 14C. Toxicology and Applied Pharmacology 43 303-315... 

With the synthesis of the doubly labeled radioactive compound,34 5-formyl-14C-tetrahydrofolate-3H, investigators have been able to trace the metabolic products when the drug is administered orally or intravenously.50... 

Expired air. For 14C-labeled chemicals, the tracer carbon may be incorporated in vivo into carbon dioxide, a possible metabolic product. Therefore, when the position of the radiolabel indicates the potential for biological instability, a pilot study to collect expired air and monitor its radioactivity content should be conducted prior to initiating a full-scale study. Expired air studies should also be performed in situations where the radiolabel has been postulated to be stable but analyses of urine and feces from the toxicokinetic study fail to yield complete recovery (mass balance) of the dose. 

When larvae were exposed to an equivalent concentration of radio-labeled naphthalene complexed with bovine serum albumin (BSA), the maximum value for accumulated metabolites was 21%. Radio-labeled naphthalene was almost entirely depurated in 24-36 hr, whereas metabolic products were strongly resistant to depuration... 

Little is known on the metabolic fate of l-methylpyrrolidin-2-one (5.60), an industrial solvent also useful as a solubilizing agent and a penetration enhancer in topical formulations. A preliminary investigation of the disposition and metabolism of labeled l-methylpyrrolidin-2-one in the rat showed that the compound is excreted mainly in urine [171]. Three urinary metabolites were detected, the major of which (ca. 15% of the dose) was 4-(methylami-no)but-2-enoic acid (5.61). This unsaturated product may likely have been formed by H20 elimination from a hydroxylated metabolite. 

The quantitative analysis was performed with the technique of gas chromato-graphy/mass spectroscopy. A radioactive sample of Cisobitan , which was labelled with 14C at the geminal methyl groups and which was hexadeuterated in the 4,4-dimethyl-siloxy position, was used for this investigation. Silylation of the metabolic products was carried out with hexamethyldisilazane. 

An earlier version of the DIDB was described in Chapter 14 of the previous edition of this book (5). The new DIDB application launched in 2005 has a typical multitier architecture in a Microsoft . NET environment. The back end is a Microsoft SQL Server 2000 and the current application is deployed on a Web farm. Currently, the database has data extracted from more than 6280 published articles (1966 to 2007) related to drug metabolism and DIs and 260 product labels (1998 to 2007). The use of the Web facilitates worldwide access as well as upgrades and updates the DIDB is updated daily. 

The title compound, l-[bis-(4-fluorophenyl)methyl]-4-(3-phenylpropenyl) piperazine, 123, clinically used as a calcium channel blocker of the piperazine class166, has been labelled with 18F by alkylation of Af-cinnamylpiperazine with 4-[18F]fluoro-4 -fluoroben-zhydryl chloride 124 (equation 73)167. The biodistribution of 123, its effect on the dopamine reuptake blockers and metabolic products are under investigation167. 

Intracellular fluxes can be estimated more precisely through 13C tracer experiments. Following 13C feeding to a cell it is possible to analyze metabolic products, such as amino acids, and measure 13C enriched patterns, so to be able to reconstruct the flux distribution from the measured data [91]. To obtain flux data from the labeling patterns, two techniques can be applied NMR [92, 93] and MS [94, 95]. Due to the low intracellular concentration of metabolites, these are often difficult to measure therefore the analysis of the labeling pattern of amino acids in proteins is used as input for flux quantification. Here proteins are hydrolyzed to release labeled amino acids and further analyzed by NMR of GC-MS. Once NMR or MS spectra are recorded, the next step is the quantitative interpretation of the isotopomer data by using mathematical models that describe the relationship between fluxes and the observed isotopomer abundance [96, 97], Some of the mathematical approaches used include cumulative isotopomer (cumomers) [98], bondomers [99], and fractional labeling [100], For a more comprehensive review on the methods we refer to Sauer [91]. 

The belladonna alkaloids are absorbed rapidly after oral administration (75). They enter the circulation when applied locally to the mucosal surfaces of the body. Atropine absorbed from inhaled smoke of medicated cigarettes can abolish the effects of intravenous infusion of methacholine in humans. The transconjunctival absorption of atropine is considerable. About 95% of radioactive atropine is absorbed and excreted followingsubconjunctival injection in the rabbit. The total absorption of quaternary ammonium derivatives (Section 3.5) of the alkaloids after an oral dose is only about 25%. The liver, kidney, lung, and pancreas are the most important organs that take up the labeled atropine. The liver probably excretes metabolic products of atropine by way of bile into the intestine (in mice and rats). 

While in an experiment with tritium labeled triamcinolone in the dog Florini, et.al. identified 6P-hydroxytriamcinolone as the major metabolic product, no triamcinolone acetonide metabolic products have been reported thus far. 

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