Metabolic Degradation Rates

According to Table 13.2.2, the two enol ethers (azoxystrobin and picoxystrobin) and the methoxycarbamate pyraclostrobin rank next, thus forming a cluster of strobilurins with intermediate degradation speeds. 

The highest metabolic stabilities are seen with the oximino amides (orysastro-bin, metominostrobin and dimoxystrobin) and with the dihydrodioxazine (fluox-astrobin). This high level of stability is one of several prerequisites for applications where long-lasting fungicidal efficacy should be maintained while the active compound is intensively exposed to plant metabolic processes, e.g., after root uptake in rice. 

At this point, I want to present a somewhat farcical - but not entirely ludicrous - quantitative structure-activity relationship (QSAR) Each of the nine commer- 

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Metabolic degradation rates vary widely between species (Table 19.2). 

Metabolism studies conducted on 6 showed that 0-dealkylation of one heterocycle methoxy group was occurring in rice (Fig. 2.4.3) [47]. A comparison of metabolic degradation rates and activity on indica rice, japonica rice and bamyardgrass for 6 indicates that degradation rates explain the major differences observed in activity (Table 2.4.6). Other factors, such as site of uptake and transport, which are modulated by plant structure and metabolism, may contribute to additional rice selectivity observed for penoxsulam. 

PAHs are widely distributed in the environment as evidenced by their detection in sediments, soils, air, surface waters, and plant and animal tissues. However, the ecological impact of PAHs is uncertain. PAHs show little tendency for bioconcentration despite their high lipid solubility (Pucknat 1981), probably because most PAHs are rapidly metabolized. Sims and Overcash (1983) list a variety of research needs regarding PAHs in soil-plant systems. Specifically, research is needed to establish the rates of PAH decomposition in soils the soil PAH levels above which PAH constituents adversely affect the food chain and enhancement factors that increase degradation rates of PAHs, especially PAHs with more than three rings. Once these factors have been determined, PAH disposal into soils may become feasible at environmentally nonhazardous levels. 

Whereas cyclamate as such is not metabolised in the human body, bacteria in the intestinal tract may degrade cyclamates to cyclohexylamine. The degradation rates vary widely and may occasionally exceed 50%, but are generally limited to a few percent of the total intake, should any metabolism occur at all. Changes within the same individual within fairly short periods have been observed. 

These results indicate that our scaled-up model ecosystems are more useful for studying system processes than processes that function in individual components of the environment. In this regard, a preliminary large scale ecosystem study could be very useful to indicate parameter limits such as overall degradation rates and likely concentrations of parent compounds plus metabolites over time. Such information would be useful in the design of metabolic studies in various components of the ecosystem. In addition, the large scale ecosystem study could also be used to determine if processes derived under laboratory conditions continue to function and/or predominate when combined in a complex system. 

Jl, J4, T6). Little benefit can be demonstrated at lower plasma levels. In one study adjustment of dosage to maintain steady-state plasma theophylline levels within a recommended optimum therapeutic range of 10-20 /ig/ml led to improved therapeutic control (J4). To achieve this a more than 8-fold difference in the daily dose was necessary (J4), due to variations between one subject and another in the rate of metabolic degradation of theophylline. 

The metabolic degradation of local anesthetics depends on whether the compound has an ester or an amide linkage. Esters are extensively and rapidly metabolized in plasma by pseudochoUnesterase, whereas the amide linkage is resistant to hydrolysis. The rate of local anesthetic hydrolysis is important, since slow biotransformation may lead to drug accumulation and toxicity. In patients with atypical plasma cholinesterase, the use of ester-linked compounds, such as chloroprocaine, procaine and tetracaine, has an increased potential for toxicity. The hydrolysis of all ester-linked local anesthetics leads to the formation of paraaminobenzoic acid (PABA), which is known to be allergenic. Therefore, some people have allergic reactions to the ester class of local anesthetics. 

Effects on growth and calorigenesis are accompanied by a pervasive influence on metabolism of drugs as well as carbohydrates, fats, proteins, and vitamins. Many of these changes are dependent upon or modified by activity of other hormones. Conversely, the secretion and degradation rates of virtually all other hormones, including catecholamines, cortisol, estrogens, testosterone, and insulin, are affected by thyroid status. 

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