Sulfoxidation carbamate metabolism

The carbamate insecticide aldicarb (Figure 2.13) that exerts its effect by inactivating acetylcholinesterase is metabolized by a flavin monooxygenase from rainbow trout to the sulfoxide, which is a more effective inhibitor (Schlenk and Buhler 1991). 

Albendazole is a benzimidazole carbamate. After oral administration, it is erratically absorbed (increased with a fatty meal) and then rapidly undergoes first-pass metabolism in the liver to the active metabolite albendazole sulfoxide. It reaches variable maximum plasma concentrations about 3 hours after a 400-mg oral dose, and its plasma half-life is 8-12 hours. The sulfoxide is mostly protein-bound, distributes well to tissues, and enters bile, cerebrospinal fluid, and hydatid cysts. Albendazole metabolites are excreted in the urine. 

In ruminants, oral doses of albendazole are readily absorbed from the gut. Following absorption, albendazole undergoes extensive metabolism by rapid first-pass oxidation of its sulfoxide group to form albendazole sulfoxide, then further oxidation to form albendazole sulfone, and by deacetylation of the carbamate group to form albendazole-2-aminosulfone. Albendazole sulfoxide, albendazole sulfone, and albendazole-2-aminosulfone are the main metabolites found in tissues, whereas other minor metabolites have been also detected at much lower concentrations. 

Carbamates such as Aldicarb undergo degradation under both aerobic and anaerobic conditions. Indeed the oxidation of the sulfur moiety to the sulfoxide and sulfone is part of the activation of the compound to its most potent form. Subsequent aerobic metabolism can completely mineralize the compound, although this process is usually relatively slow so that it is an effective insecticide, acaricide and nematocide. Anaerobically these compounds are hydrolyzed, and then mineralized by methanogens (61). 

N-methyl carbamates do not need activation to inhibit ChEs. However, at least in the case of aldicarb, inhibition increases with metabolism. Aldicarb is rapidly oxidized to the relatively stable aldicarb sulfoxide, which in turn is more slowly metabolized to aldicarb sulfone, a stronger AChE inhibitor. These products are then detoxified by conversion to oximes and nitriles, which in turn are degraded to aldehydes, acids, and alcohols. Procarbamate derivatives were... 

The relative amounts of the N-depropyl EPTC both early in the incubation period and later suggest that hydroxylation of the a-propyl carbon of the N,N-dialkyl moiety is a major route in the microbial metabolism of EPTC. Hydroxylation of the other carbons of the N,N-dialkyl portion of the carbamate was found to be a less preferred route compared to the hydroxylation of the a-propyl carbon. Sulfoxidation of the carbamate may be second in the importance to the hydroxylation reactions observed. 

Methods have also been developed for specific classes of pesticides. N-methylcarbamates are systemic insecticides characterized by moderate polarity and relatively low thermal stability. For these reasons, LC methods are more suitable than GC methods for the analysis of environmental samples. In the case of aldicarb, metabolic pathways involve oxidative conversion to aldicarb sulfoxide and aldicarb sulfone. These fransformafion products are reportedly more toxic and persistent than the parent compound [83] and are important to monitor along with the parent compound. One of the first LC methods for the determination of carbamate pesticides and their transformation products is based on LC... 

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