Excretion, free

Oral treatment of sheep and cattle (Bos spp.) with diflubenzuron is followed by absorption of the compound through the gastrointestinal tract, metabolism, and elimination of residues through the urine, feces, and, to a very limited extent, milk. Intact diflubenzuron is eliminated in the feces of orally dosed cattle and sheep (Ivie 1978). Major metabolites of diflubenzuron excreted by cattle and sheep result from hydroxylation on the difluorobenzoyl and chlorophenyl rings, and by cleavage between the carbonyl and amide groups to produce metabolites that are excreted free or as conjugates (Ivie 1978). Cattle dosed repeatedly with diflubenzuron had detectable residues only in liver... 

Hunn (28) showed that rainbow trout which were anesthetized with MS-222 excreted free and acetylated forms of the drug renally (Figure 1). MS-222 injected intraperitoneally was also excreted... 

Pharmacology Wilson disease (hepatolenticular degeneration) is an inherited metabolic defect resulting in excess copper accumulation, possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper, but when their capacity is exceeded, copper is released into the blood and is taken up into extrahepatic sites. Treat this condition with a low copper diet and chelating agents that bind copper to facilitate its excretion from the body. Trientine is a chelating compound for removal of excess copper from the body. 

The metabolism of aldosterone is similar to that of cortisol, about 50 mcg/24 h appearing in the urine as conjugated tetrahydroaldosterone. Approximately 5-15 mcg/24 h is excreted free or as the 3-oxo glucuronide. 

In an early study, rats, guinea pigs, dogs, and rabbits exposed to 100-400 ppm 2-butoxyethanol for 4 hours excreted free 2-butoxyacetic acid in the urine (Carpenter et al. 1956). Dogs and monkeys exposed to 100-398 ppm 2-butoxyethanol for 28-90 days also excreted free 2-butoxyacetic acid in the urine. These data indicate that the metabolism of 2-butoxyethanol to 2-butoxyacetic acid is a common pathway in mammalian species. 

Glucocorticoids also exert effects on fluid and electrolyte balance, largely due to permissive effects on tubular function and actions that maintain glomerular filtration rate. In part, the inability of patients with glucocorticoid deficiency to excrete free water results from the increased secretion of vasopressin, which stimulates water reabsorption in the kidney. 

J.T., Oxidative DNA damage in vivo relationship to age, plasma antioxidants, dmg metabohsm, glutathione-S-transferase activity and urinary creatinine excretion. Free Radic. Res., 29, 565, 1998. 

Screening B. 5 ml narcotic analgesics and S-block-ers excreted free and/or conjugated - basic hydrolysis - liquid-liquid extraction, concentration -trimethylsilyl (TMS) derivatization - GC-MS full scan analysis ... 

DHBs after absorption distribute rapidly and widely among tissues but bio accumulation is low (121). They are metabolized to their respective benzoquinone and then detoxified by conjugation and excreted in the urine mainly as conjugates. Some deconjugations may occur in the urine. Resorcinol is also excreted in the urine in a free and conjugated state, essentially glucuronide and sulfate. 

Only the small amounts of T and T that are free in the circulation can be metabolized. The main route is deiodination of T to T and i-T, and from these to other inactive thyronines (21). Most of the Hberated iodide is reabsorbed in the kidney. Another route is the formation of glucuronide and sulfate conjugates at the 4 -OH in the Hver. These are then secreted in the bile and excreted in the feces as free phenols after hydrolysis in the lower gut. 

Materials may be absorbed by a variety of mechanisms. Depending on the nature of the material and the site of absorption, there may be passive diffusion, filtration processes, faciHtated diffusion, active transport and the formation of microvesicles for the cell membrane (pinocytosis) (61). EoUowing absorption, materials are transported in the circulation either free or bound to constituents such as plasma proteins or blood cells. The degree of binding of the absorbed material may influence the availabiHty of the material to tissue, or limit its elimination from the body (excretion). After passing from plasma to tissues, materials may have a variety of effects and fates, including no effect on the tissue, production of injury, biochemical conversion (metaboli2ed or biotransformed), or excretion (eg, from liver and kidney). 

Esmolol is iv adrninistered. Maximal P-adrenoceptor blockade occurs in 1 min. Its elimination half-life is about 9 min. EuU recovery from P-adrenoceptor blockade is within 30 min after stopping the infusion. The therapeutic plasma concentrations are 0.4—1.2 lg/mL. It is metabolized by hydrolysis in whole blood by red blood cell esterases resulting in the formation of a primary acid metabohte and free methanol. The metabohte is pharmacologically inactive. The resulting methanol levels are not toxic. Esmolol is 55% bound to plasma protein, the acid metabohte only 10%. Less than 2% of parent dmg and the acid metabohte are excreted by the kidneys. Plasma levels may be elevated and elimination half-hves prolonged in patients with renal disease (41). 

Citric acid occurs widely in the plant and animal kingdoms (12). It is found most abundantiy in the fmits of the citms species, but is also present as the free acid or as a salt in the fmit, seeds, or juices of a wide variety of flowers and plants. The citrate ion occurs in all animal tissues and fluids (12). The total ckculating citric acid in the semm of humans is approximately 1 mg/kg body weight. Normal daily excretion in human urine is 0.2—1.0 g. This natural occurrence of citric acid is described in Table 7. 

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

Water solubility (polarity) is essential for excretion. Even though lipid-soluble compounds may also be excreted to primary urine, they are usually at least partially reabsorbed. The metabolites formed in the liver and extrahe-patic tissues remain free (i.e., not bound to proteins) and are, therefore, readily excreted. 

Amino Acids. Early observations on the liberation of amino acids by plant roots were reviewed by Loehwing (94), Rademacher (121), and Borner (12). Free amino acids have been isolated from soil fractions (119), and the excretion of a variety of ninhydrin-positive compounds by plant roots has been demonstrated under controlled conditions by Katznelson et al. (18), Rovira (121), and Pearson and Parkinson (115). 

Carbonic anhydrase is an enzyme that produces free hydrogen ions, which are then exchanged for sodium ions in the kidney tubules. Carbonic anhydrase inhibitors inhibit the action of the enzyme carbonic anhydrase This effect results in the excretion of sodium, potassium, bicarbonate, and water. Carbonic anhydrase inhibitors also decrease the production of aqueous humor in the eye, which in turn decreases intraocular pressure (IOP) (ie, the pressure within the eye). 

Opioids are easily absorbed subcutaneously and intramuscularly, as well as from the gastrointestinal tract, nasal mucosa (e.g., when heroin is used as snuff), and lung (e.g., when opium is smoked). About 90% of the excretion of morphine occurs during the first 24 hours, but traces are detectable in urine for more than 48 hours. Heroin (diacetyhnorphine) is hydrolyzed to monoacetylmorphine, which is then hydrolyzed to morphine. Morphine and monoacetylmorphine are responsible for the pharmacologic effects of heroin. Heroin produces effects more rapidly than morphine because it is more lipid soluble and therefore crosses the blood-brain barrier faster. In the urine, heroin is detected as free morphine and morphine glucuronide (Gutstein and Akil 2001 Jaffe et al. 2004). 

Monteiro, L.R. and Furness, R.W (2001). Kinetics, dose-response, excretion and toxicity of methyl mercury in free living Cory s shearwater chicks. Environmental Toxicology and Chemistry 20, 1816-1824. 

Parker, R. J., Priester, E. R., and Sieber, S. M. (1982). Comparison of lymphatic uptake metabolism, excretion, and biodistribution of free and liposome-entrapped (l cjcytosine beta-D-arabinofuranoside following intraperitoneal administration in rats, Drug. Me tab. Dispos., 10, 40-46. 

Kidney Excretion and glu-coneogenesis Gluconeogenesis Free fatty acids, lactate, glycerol Glucose Glycerol kinase, phosphoenolpyruvate carboxy kinase... 

Copper is an essential trace element. It is required in the diet because it is the metal cofactor for a variety of enzymes (see Table 50—5). Copper accepts and donates electrons and is involved in reactions involving dismu-tation, hydroxylation, and oxygenation. However, excess copper can cause problems because it can oxidize proteins and hpids, bind to nucleic acids, and enhance the production of free radicals. It is thus important to have mechanisms that will maintain the amount of copper in the body within normal hmits. The body of the normal adult contains about 100 mg of copper, located mostly in bone, liver, kidney, and muscle. The daily intake of copper is about 2—A mg, with about 50% being absorbed in the stomach and upper small intestine and the remainder excreted in the feces. Copper is carried to the liver bound to albumin, taken up by liver cells, and part of it is excreted in the bile. Copper also leaves the liver attached to ceruloplasmin, which is synthesized in that organ. 

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