Gastrointestinal system excretion

Sato et al. (1991) expanded their earlier PBPK model to account for differences in body weight, body fat content, and sex and applied it to predicting the effect of these factors on trichloroethylene metabolism and excretion. Their model consisted of seven compartments (lung, vessel rich tissue, vessel poor tissue, muscle, fat tissue, gastrointestinal system, and hepatic system) and made various assumptions about the metabolic pathways considered. First-order Michaelis-Menten kinetics were assumed for simplicity, and the first metabolic product was assumed to be chloral hydrate, which was then converted to TCA and trichloroethanol. Further assumptions were that metabolism was limited to the hepatic compartment and that tissue and organ volumes were related to body weight. The metabolic parameters, (the scaling constant for the maximum rate of metabolism) and (the Michaelis constant), were those determined for trichloroethylene in a study by Koizumi (1989) and are presented in Table 2-3. 

See also Absorption Blood Developmental Toxicology Excretion Gastrointestinal System Kidney Liver Metal-lothionein Neurotoxicity Pharmacokinetics/Toxicokinet-ics Skeletal System. 

Homeostasis of magnesium is tightly regulated and depends on the balance between intestinal absorption and renal excretion. Thirty-to-forty percent of ingested magnesium is absorbed from the gastrointestinal system, mostly by the small bowel. Most of the magnesium in the body is stored intracellularly or... 

Triazine compounds are generally well absorbed in the gastrointestinal system. When administered by the oral route, the greatest concentrations of prometryn are found in the blood, spleen, and lungs. Dermal absorption is relatively high, with 7-15% of the material applied to skin being absorbed. Prometryn is excreted in urine or feces within 72 h. It is extensively metabolized, with less than 2% of the parent material appearing in the urine or feces. 

The limited available toxicokinetic data show that RDX is absorbed through the gastrointestinal system, lungs, and skin, and is distributed to the cerebrospinal fluid, plasma, urine, and feces. No information is available on the metabolism of RDX, and it appears to be excreted in the urine and feces following oral exposure. No further information is available on the mechanisms of action of RDX in either humans or animals. 

Uncoupled iodide is excreted via the urine (70%) and a minor part is excreted via the gastrointestinal system. 

Abnormally high amounts of phosphate, if suddenly introduced into the gastrointestinal system, are rapidly excreted through cathartic action. 

These studies represent the first report of the metabolism of brevetoxins by mammalian systems. PbTx-3 was rapidly cleared from the bloodstream and distributed to the liver, muscle, and gastrointestinal tract. Studies with isolated perfused livers and isolated hepatocytes conflrmed the liver as a site of metabolism and biliary excretion as an important route of toxin elimination. [ H]PbTx-3 was metabolized to several compounds exhibiting increased polarity, one of which appeared to be an epoxide derivative. Whether this compound corresponds to PbTx-6 (the 27,28 epoxide of PbTx-2), to the corresponding epoxide of PbTx-3, or to another structure is unknown. The structures of these metabolites are currently under investigation. 

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. 

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. 

Chemically, arsenic is complex in that it can exist in a variety of forms including trivalent and pentavalent or as arsenic trioxide (computer chip manufacture) and arsenic acid. Arsenic is excreted in skin cells, sweat, hair, and fingernails, which can be seen as white transverse bands. Acute exposure to arsenic results in gastrointestinal pain, sensory loss, cardiovascular failure, and death. Chronic exposure or survival of acute exposure can cause loss of peripheral sensory function and loss of central nervous system function. Chronic arsenic exposure can also cause cancer of the lung and skin (see the chapter on arsenic). 

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. 

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