Sulphide metabolite

Half-life. Plasma half-life, sulindac about 7 hours, sulphide metabolite about 16 to 18 hours. 

The precise mechanism of action of the drug is still unknown. However, it is believed that the sulphide metabolite may perhaps inhibit the prostaglandin synthesis. Interestingly, it exerts appreciably much less effect on the platelet function and bleeding time in comparison to aspirin it must be used with great caution in such patients who could be affected quite adversely by this sort of action. 

The drug gets absorbed invariably to the extent of 90% after the oral administration. The peak plasma levels are usually accomplished in about 2 hour in the fasting patient and may be extended between 3-4 hours when given with food. It has been duly observed that the mean half-life of sulindac is 7 = 8 hours and the mean half-life of the corresponding sulphide-metabolite is 16.4 hour (almost double than the parent drug). 

In 6 healthy subjects colestyramine 4 g twice daily with meals was found to reduce the AUC of a simultaneous single 400-mg dose of sulindac by 78% the AUC of its sulfide metabolite was reduced by 84%. Even when the sulindac was given 3 hours before the colestyramine, its AUC of colestyramine and its sulphide metabolite were reduced by 44% and 55%, respectively. ... 

The combined RIA-technique and isotope dilution has been successfully developed to estimate SULINDAC along with its two prominent metabolites, namely its sulphone and its sulphide present in the plasma-level as shown in the following chemical structures X and Y. 

Reversible reduction to sulphide and oxidation to sulphone + unidentified metabolite... 

To underscore the utility of accurate mass analysis for distinguishing isomeric metabolites, the metabolism of rabeprazole (used as an inhibitor of gastric acid secretion, marketed under the tradename Aciphex ) is considered. Following incubation of rabeprazole with microsomes, two metabolites with nominal m/z of 344 are formed (Miura et al., 2006 Setoyama et al., 2006). These metabolites, shown below, are the aldehyde (m/z 344.1069) and sulphide (m/z 344.1433) metabolites of rabeprazole ... 

As shown in Fig. 4.8, the mass difference between the two metabolites is 36.4 mDa and a mass spectrometer with a resolving power of at least 9500 (M/AM = 344/ 0.0364 = 9450) is required to separate between these two metabolites. MS/MS fragmentation combined with accurate mass measurement is the preferred method for structural elucidation of metabolites, especially when it can help to correlate the elemental composition determined in the MS mode. In the example shown in Fig. 4.8, exact mass measurements of the precursor ions are used as lock mass to measure the exact mass of each fragment ion. Exact mass measurements of the fragment ion at m/z 226 help to narrow down the sites of modifications and allows one to distinguish between rabeprazole-sulphide and rabeprazole-aldehyde. 

Quantification. High Pressure Liquid Chromatography. In plasma or urine sulindac and its sulphide and sulphone metabolites, sensitivity 100 ng/ml in plasma, UV detection—B. 

Gas Chromatography-Mass Spectrometry. In plasma or urine sulphide and / -hydroxysulphide metabolites, detection limit 5 ng/ml for sulphide and 30 ng/ml forp-hydroxysulphide— P. Jakobsen and A. Kirstein Pedersen, J. Pharm. Pharmac., 1981, ii, 89-92. 

Disposition in the Body. Readily absorbed after oral administration. It is metabolised by reduction to the sulphide which is active and is the predominant circulating metabolite, reaching a concentration about 25% of that of sulphinpyrazone. It is also oxidised to the sulphone (active) and there are several hydroxy metabolites. All metabolites are excreted in the urine as the C-glucuronides, only a small proportion being excreted in... 

Sulforal, 992 Sulforidazine, 980 (metabolite), 738, 1020 Sulformethoxine, 978 Sulforthomidine, 978 Sulfotrimin, 988 Sulfuno, 991 Sulginum, 986 Sulindac, 981 Sulindac sulphide, 981 Sulindac sulphone, 981 Sulla, 989 Sulmycin, 637 Sulpha..., see also under Sulphacalyre, 981 Sulphacarbamide, 995 Sulphacetamide, 981 Sulphacetamide sodium, 981 Sulphacetamide, soluble, 981 Sulphachlorpyridazine, 982 Sulphadiazine, 982 Sulphadiazine sodium, 983 Sulphadiazine, soluble, 983 Sulphadimethoxine, 983 Sulphadimethyloxazole, 991 Sulphadimethylpyrimidine, 984... 

Sulphanilylacetamide, 981 Sulphanilylurea, 995 Sulphaphenazole, 992 Sulphaphenylpyrazol, 992 Sulphapyridine, 992 (metabolite), 994 Sulphapyridine sodium, 993 Sulphapyridine, soluble, 993 Sulphaquinoxaline, 980 Sulphasalazine, 993 Sulphasomidine, 994 Sulphasomizole, xvii Sulphate conjugation, 291 Sulphathiazole, 995 (metabolite), 900, 978 Sulphathiazole sodium, 995 Sulphathiazole, soluble, 995 Sulphatriad, 979, 982, 995 Sulphaurea, 995 Sulphide, 68 Sulphinpyrazone, 996 Sulphinpyrazone sulphide, 996 Sulphinpyrazone sulphone, 996 Sulphonal, xvii Sulphonamides, colour test, 131 gas chromatography, 200... 

Omeprazole is rapidly and completely metabolized after intestinal absorption. Oxidative processes for metabolism are predominant and three main metabolites of omeprazole have been identified the corresponding sulphone and sulphide as well as hydroxyomeprazole. Omeprazole sulphone is further metabolized or it is eliminated in the faeces. Renal excretion is the predominant route of elimination of omeprazole metabolites [20, 28, 110]. The metabolism of lansoprazole in humans is comparable to that of omeprazole it is converted to hydroxylansoprazole, lansoprazole-sulphone, lansoprazole-sulphide and the hydroxylated sulphone [111]. 

This series of KCAs, developed originally from a study of potential K /H ATPase inhibitors resulted in the lead compound RP 49356 (4), and its biologically active IR,2R enantiomer, aprikalim (5) (see Figure 9.1) [41]. The precursor sulphide of (4) was inactive in vitro, but careful observation of its effect in SHR identified a delayed onset in antihypertensive activity that led to the identification of the trans sulphoxide as its active metabolite. In contrast, the cis diastereomer was significantly less active. 

While all NSAIDs have the potential for inducing renal failure, there has been speculation of quantitative differences among the individual NSAIDs. Sulindac was thought to be renal sparing, possibly because of its unusual metabolic pathway [29, 77-79]. The parent compound, sulindac sulphoxide, is an inactive prodrug, which undergoes hepatic metabolism to sulindac sulphide, the metabolite responsible for its anti-inflammatory activity. Sulindac sulphoxide is also metabolized to a much lesser extent to an inactive metabolite, sulindac sulphone. It was hypothesized that, within the human kidney, sulindac sulphide was reversibly oxidized to the inactive parent compound, sulindac sulphoxide, with the result that renal prostaglandin production was not perturbed [29, 78]. 

A wide variety of organic and inorganic compounds inhibit microbial activity by interfering with the uptake of metabolites and enzymic reactions (Davis and Feingold, 1962 Pelczar and Reid, 1958). In particular, the heavy metals are extremely toxic to the heterotrophs but are tolerated at higher levels by Desulfovibrio spp. due to their precipitation as metal sulphides (see p. 343). Other factors affecting the activity of sulfate-reducers are discussed in Chapter 6.1. 

Phase I metabolites of some drugs have activity exceeding or at least equal to that of the parent drug. Examples include phenobarbital (from primidone), ciprofloxacin (from enrofloxacin), desfuroylceftiofur (from ceftiofur) and possibly benzimidazole sulphoxides (from the corresponding sulphides). 

Albendazole and fenbendazole, prochiral sulphide benzimidazole anthelmintics, are metabolically converted (sulphoxidation) to the corresponding active sulphoxide metabolites, each of which exists in the plasma as two enantiomers. Sulphoxide benzimidazoles have a chiral centre around the sulphur atom in their molecules. The sulphoxide metabolites (enantiomers) are irreversibly metabolized (sulphonation) to inactive sulphones. This pathway of hepatic biotransformation has been shown to occur both in ruminant (sheep, goats, cattle) and monogastric (man, dogs, rats) species (Delatour et al., 1991b,... 

Several bacterial groups produce potentially detrimental metabolites such as inorganic acids (e.g., Acidithiobacillus thiooxidans), organic acids (most bacteria, algae, and fungi), sulphide (sulphate-reducing bacteria), and ammonia, as discussed above. 

In addition to a series of problems/ two main problems resulting from bacterial growth in offshore structures are [20] (1) hydrogen sulphide production (generated, for example, by SRB) that besides being volatile and toxic, thus serious to the personnel safety, causes corrosion and souring of the products (crude oil, for instance) which ultimately affects the quality and final price [21], and (2) the production of bacterial metabolites which could give rise to accelerated materials deterioration. 

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