Excretory processes

Excretory processes for xenobiotics are best understood for mammals, with far less work having been done on birds, reptiles, and amphibians. Highly lipophilic compounds show little tendency to be excreted unchanged. In the absence of effective metabolism, they tend to have very long biological half-lives in depot fat. Thus, half-lives of about 1 year have been reported for p,p -DDE in birds, whereas higher... 

Some minor routes of excretion exist sweat, hair, saliva, semen, milk. While these routes out of the body do not count for much as excretory processes, excretion of some chemicals into milk can be important because it constitutes an exposure pathway for infants, if the milk is from their mothers, and for many people if it is from dairy cattle. Many fat-soluble chemicals follow this pathway out of the body, dissolved in the fatty portion of the milk. Excretion of chemicals through milk is common enough to prompt considerable attention from toxicologists. 

Finally, compounds that undergo active tubular secretion also are filtered at the glomerulus (assuming protein binding is minimal). Hence, a reduction in secretory activity does not reduce the excretory process to zero but rather to a level that approximates the glomerular filtration rate. 

The oximes, although they are metabolized to some extent, are removed from the body largely by excretory processes. Particularly for the monopyridinlum monoxlmes, the kidneys are important excretory organs. Renal insufficiency has been found to increase the toxicltles of these oximes significantly, but to have no definite effect on that of the ketoxime. 

The concept of clearance is useful in pharmacokinetics because clearance is usually constant over a wide range of concentrations, provided that ehmination processes are not saturated. Saturation of biotransformation and excretory processes may occur in overdose and toxic okinetic effects should be considered. If a constant fraction of drug is eliminated per unit time, the elimination follows first-order kinetics. However, if a constant amount of drug is eliminated per unit time, the elimination is described by zero-order kinetics. Some drugs, for example, ethanol, exhibit zero-order kinetics at normal or non-intoxicating concentrations. However, for any drug that exhibits first-order kinetics at therapeutic or nontoxic concentrations, once the mechanisms for elimination become saturated, the kinetics become zero order and clearance becomes variable.3... 

Similarly, in the case of renal disease, Giacomini and others have clearly demonstrated the stereoselectivity of renal drug excretory processes (14,27). Again with decreased renal function, including glomerular filtration, proximal reabsorption, and secretion, no information is available to determine whether the stereoselective processes decline in parallel with nonstereoselective mechanisms, such that after the administration of a racemic drug, the isomeric ratio in plasma remains the same. 

The biochemical composition of mine varies considerably from species to species and also with the age of the animal as almost all species have age-related changes in renal function. Rats and other rodents have much higher levels of taurine, citrate, succinate, 2-oxoglutarate and allantoin than humans and this is clearly apparent in the H NMR spectra. Rat urine (and that of other rodents) is generally much more concentrated than human urine, and so NMR signal-to-noise ratios may be better for many metabolites. All animals have physiological processes which are modulated by biological rhythms. This includes excretory processes and the urinary composition of an... 

The association between hyperphosphatasemia and hepatobiliary disorders was first reported in 1930 (R24) and until the late 1960s, this association was explained in terms of the excretion theory. According to this theory, skeletal alkaline phosphatase is normally excreted by the liver and failure of this excretory process, as in biliary obstruction, results in serum alkaline phosphatase elevation (G28). 

Fig. 11. Partial obstruction of the bile passages (as in patients with cholan olar carcinoma or hepatic metastases) enhances alkaline phosphatase synthesis proximal to the site of obstruction. Such patients may have normal serum bilirubin values because the excretory processes in other parts of the liver are unimpaired.

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