Gastrointestinal tract excretion into

The most important route of excretion for most non-gaseous or non-volatile compounds is through the kidneys into the urine. Other routes are secretion into the bile, expiration via the lungs for volatile and gaseous substances, and secretion into the gastrointestinal tract, or into fluids such as milk, saliva, sweat, tears and semen. 

Toxicity. Fluoroborates are excreted mostly in the urine (22). Sodium fluoroborate is absorbed almost completely into the human bloodstream and over a 14-d experiment all of the NaBF ingested was found in the urine. Although the fluoride ion is covalently bound to boron, the rate of absorption of the physiologically inert BF from the gastrointestinal tract of rats exceeds that of the physiologically active simple fluorides (23). 

Only a small (ca 3%) fraction of ingested or inhaled manganese is absorbed, which occurs primarily by the intestines (209). Once absorbed, manganese is regulated by the Hver, where it is excreted into the bile and passes back into the intestine, where some reabsorption may occur (210). Manganese is elirninated almost exclusively (>95%) by the bile in the gastrointestinal tract. 

Diquat and paraquat are quaternary ammonium compounds largely used as contact herbicides and crop desiccants. When systemic absorption occurs, paraquat and diquat are rapidly distributed into the body. Paraquat primarily accumulates in the lungs and kidneys, while the highest diquat concentrations have been found in the gastrointestinal tract, liver, and kidneys (WHO, 1984). Urine is the principal route of excretion for both diquat and paraquat, which are primarily eliminated as unmodified compounds. Occupationally exposed workers can be monitored by measuring paraquat and diquat concentrations in urine samples (Table 6). Blood concentrations are useful to monitor acute poisoning cases. 

Inorganic lead ions are not known to be metabolized in the body but they are complexed by macromolecules. Lead that is not retained in the body is excreted principally by the kidney as salts or through biliary clearance into the gastrointestinal tract in the form of organometallic conjugates. 

Cartwright [124] reported that miconazole was slightly absorbed from epithelial and mucosal surface. The drug is well absorbed from the gastrointestinal tract, but caused nausea and vomiting in some patients. The drug may be given intravenously but was associated phlebitis. Up to 90% of the active compound was bound to plasma protein. Distribution into other body compartments was poor. Metabolism was primarily in the liver, and only metabolites were excreted in the urine. At therapeutic levels, they were relatively nontoxic both locally and systematically, but occasionally produced disturbances on the central nervous system. 

Only 6% of the radioactivity from radiolabeled ( "C) heptachlor was found in the urine while 60% was found in the feces of male rats 10 days after a single oral dose indicating that most of the radioactive material was not absorbed and was excreted in the feces (Tashiro and Matsumura 1978). These data strongly suggest that a large percentage of heptachlor is absorbed from the gastrointestinal tract and eliminated via the bile into the feces. More than 72% of the radioactivity eliminated in the feces was present as metabolites of heptachlor (heptachlor epoxide, 13.1% H-2, < 0.1% 1-OH-chlordene, 19.5% 1-OH-chlordene epoxide, 17.5% 1,2-OH-chlordene, 3.5% H-6, 19.0%). 

After oral administration, BPA is rapidly and efficiently absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism in the gut wall and hver. BPA is mainly transformed into BPA-glucuronide and to a lesser extent into BPA-sulfate. These highly water-soluble metabolites are rapidly cleared from blood by the kidneys and excreted with urine [205]. Volkel et al. determined that the terminal half-life of BPA is less than 6 h in humans [206]. 

Orally administered thiazides are rapidly absorbed from the gastrointestinal tract and begin to produce diuresis in about 1 hour. Approximately 50% of an oral dose is excreted in the urine within 6 hours. These compounds are organic acids and are actively secreted into the proximal tubular fluid by the organic acid secretory mechanism. There also appears to be an extrarenal pathway for their elimination involving the hepatic-biliary acid secretory system that is particularly important for thiazide elimination when renal function is impaired. 

Buspirone is well absorbed from the gastrointestinal tract, and peak blood levels are achieved in 1 to 1.5 hours the drug is more than 95% bound to plasma proteins. Buspirone is extensively metabolized, with less than 1% of the parent drug excreted into the urine unchanged. At least one of the metabolic products of buspirone is biologically active. The parent drug has an elimination half-life of 4 to 6 hours. 

Colchicine is rapidly absorbed after oral administration and tends to concentrate in the spleen, kidney, liver, and gastrointestinal tract. Leukocytes also avidly accumulate and store colchicine even after a single intravenous injection. Since colchicine can accumulate in cells against a concentration gradient, it is postulated that an active transport process may be involved in its cellular uptake. The drug is metabolized, primarily in the liver, by deacetylation. Fecal excretion plays a major role in colchicine elimination, since it and its metabolites are readily secreted into the bile. Only about 15 to 30% of the drug is eliminated in the urine except in patients with liver disease urinary excretion is more important in these individuals. 

Figure 3.2 Schematic of distribution and elimination of pharmaceutical compound on normal administration. Compound is distributed through the (a) lungs, (b) arteries, (c) other tissues (e.g., muscles, subcutenous tissues), (d) veins, and (e) gastrointestinal tract (i.e., oral). Notice the enteroheptic cycle where recirculation occurs between the hver and the GIT with most of the drug being excreted in the bile and is released into the gall bladder, transits into the small intestine, and is absorbed into the circulatory system.

Pharmacokinetics Rapidly absorbed from the gastrointestinal (GI) tract. Distributed into cerebrospinal fluid (CSF). Extensively and poorly metabolized in liver to dextror-phan (active metabolite). Excreted unchanged in urine. Half-life 1.4-3.9 hr (parent compound), 3.4-5.6 hr (dextrorphan). 

Pharmacokinetics Well absorbed from the gastrointestinal (Gl) tract. Widely distributed. Protein binding 50%-S>07o. Metabolized in liver as well as a certain proportion excreted into the bile and reabsorbed from the intestine. Primarily excreted in urine. Half-life Unknown. 

The entry of a compound into the bloodstream does not necessarily ensure that it wiU arrive unchanged at its specific receptor. As mentioned before, xenobiotics absorbed from the gastrointestinal tract are carried by the portal vein to the liver. The liver has a very active xenobiotic-metabohzing system in which chemicals may or may not be altered before being released through hepatic veins into the general circulation. Alternatively, they may be excreted into the bile and returned to the gastrointestinal tract. From there they may be excreted, all or in part, or reabsorbed and carried back to the liver. 

Drugs of the neomycin group are poorly absorbed from the gastrointestinal tract. After oral administration, the intestinal flora is suppressed or modified, and the drug is excreted in the feces. Excretion of any absorbed drug is mainly through glomerular filtration into the urine. 

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