Metabolites in excreta

Focus changed from metabolites accounting for >10% of the administered dose (which could potentially apply to circulating as well as metabolites in excreta) to circulating metabolites accounting for >10% of parent drug s systemic exposure. 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic substance or its metabolite(s), or the product of an interaction between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in readily obtainable body fluid(s) or excreta. However, several factors can confound the use and... 

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

Exposure. Known biomarkers of exposure to endosulfan include the measurement of endosulfan or its metabolites in tissue and excreta (Deema et al. 1966 Dorough et al. 1978 Gorbach et al. 1968) these measurements can indicate whether absorption of endosulfan has occurred. The presence of the parent compound and its metabolites are specific biomarkers for endosulfan exposure. However, no studies are available that quantify the concentrations of endosulfan or its metabolites in relation to specific environmental exposure levels. Since endosulfan induces cytochrome P450-dependent monooxygenases... 

In a study of metabolism of 14C-flocoumafen by the Japanese quail (Huckle et al. 1989), biotransformation was extensive and rapid, with eight metabolites detected in excreta. The elimination of radioactivity from the liver of Japanese quail was biphasic (Figure 11.2). After an initial period of rapid elimination, there followed a... 

A recent series of experiments with cats, chickens, or rats exposed to [uniformly labeled 14C-phenyl]-TOCP shows that a complex array of oxidized and dearylated metabolites are found in excreta and various tissues including the liver, kidney, testis, and brain (Abou-Donia et al. 1990a, 1990b Nomeir and Abou-Donia 1986 Somkuti and Abou-Donia 1990). Cats and chickens, like humans, are sensitive to TOCP-induced delayed neuropathy (Baron 1981). A similar array of oxidized and dearylated derivatives of tri-para-cresyl phosphate (but no cyclic metabolites) were identified by mass spectrometry in the urine and... 

The original entries into this class, such as chlordiazepoxide (1), were N-oxides." " Treatment of the N-acetate (2) of chlordiazepoxide with aqueous acid served to hydrolyze the acylenamine function to liberate the keto analogue (3) which has been identified in excreta as an active metabolite of 1 this... 

No visible adverse physiological effects or signs of toxicity. No effect on egg production or growth. No residues of atrazine or its metabolites detected in eggs. In excreta, however, atrazine and atrazine metabolites were detected after 24 h on treated diet and remained measurable until day 11, or after 4 days on an untreated diet (Foster and Khan 1976 Reed 1982)... 

Table 3. Relative amounts of C-heptachlor and its metabolites in fish, water and excreta, 10 days after a single injection (38.2 yg/fish).

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