Gastrointestinal excretion

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

ABSORPTION, DISTRIBUTION, AND EXCRETION Gastrointestinal (Gl) absorption of amphotericin B is negligible and intravenous dehvery is used. Amphotericin B in plasma is >90% bound to proteins. Drag elimination apparently is unchanged in anephiic patients and those on hemodialysis. Hepatic or biliary disease has no known effect on drag metabolism in humans. The terminal phase of elimination has a tj, of 15 days. Concentrations of amphotericin B in fluids from inflamed pleura, peritoneum, synovium, and aqueous humor are approximately two-thirds of plasma trough concentrations. Little amphotericin B penetrates into cerebrospinal fluid (CSF), vitreous humor, or amniotic fluid. 

In order for the feedback mechanism to be effective, the organs or systems responsible for absorption and excretion (gastrointestinal) or reabsorption and excretion (renal) must function adequately. If the intestinal track is damaged or illness causes diarrhea or vomiting, absorption and excretion of electrolytes can be affected, and the feedback mechanism will malfunction. For example, in malabsorption syndrome, electrolytes are not absorbed through the tissue of the intestines to the degree needed, even though the levels of electrolytes are low. 

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. 

Diclofenac is an exceedingly potent COX inhibitor slightly more efficacious against COX-2 than COX-1. Its absorption from the gastrointestinal tract varies according to the type of pharmaceutical formulation used. The oral bioavailability is only 30-80% due to a first-pass effect. Diclofenac is rapidly metabolised (hydroxylation and conjugation) and has a plasma half-life of 1.5 h. The metabolites are excreted renally and via the bile. 

The activity of pyrantel (Antimintii) is probably due to its ability to paralyze die helminth. Fbralysis causes die helminth to release its grip on die intestinal wall it is then excreted in die feces, pyrantel is used to treat round-worm and pinworm. Some patients receiving pyrantel may experience gastrointestinal side effects, such as nausea, vomiting, abdominal cramps, or diarrhea... 

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). 

Mescaline is considerably less potent than LSD equipotent amounts are 5 mg and 1 pg, respectively. Peyote is readily absorbed from the gastrointestinal tract. Mescaline is mainly concentrated in the liver, spleen, and kidney. Up to 60% is excreted unchanged in the urine mescaline metabolites are devoid of any psychoactive effect. 

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. 

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. 

The therapeutic dose of acamprosate is 666 mg orally three times daily, and it is supplied as a 333 mg tablet. It can be started at the full dose in most patients without titration. It differs from disulfiram and naltrexone in that it is excreted by the kidneys without liver metabolism. Consequently, it is contraindicated in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/minute), and dose reduction is necessary when the creatinine clearance is between 30 and 50 mL/minute. The most common side effects are gastrointestinal and include nausea and diarrhea. Rates of suicidal thoughts were also increased in patients treated for 1 year with acamprosate (2.4%) versus placebo (0.8%). If necessary the total daily dose maybe decreased by 1 to 3 tablets (333-999 mg) per day to alleviate side effects. 

Gout is caused by an abnormality in uric acid metabolism. Uric acid is a waste product of the breakdown of purines contained in the DNA of degraded body cells and dietary protein. Uric acid is water soluble and excreted primarily by the kidneys, although some is broken down by colonic bacteria and excreted via the gastrointestinal tract. 

Electrolytes are involved in many metabolic and homeostatic functions, including enzymatic and biochemical reactions, maintenance of cell membrane structure and function, neurotransmission, hormone function, muscle contraction, cardiovascular function, bone composition, and fluid homeostasis. The causes of electrolyte abnormalities in patients receiving PN may be multifactorial, including altered absorption and distribution excessive or inadequate intake altered hormonal, neurologic, and homeostatic mechanisms altered excretion via gastrointestinal and renal losses changes in fluid status and fluid shifts and medications. 

After doses of 10 mg/kg/day in a cow and 225 mg/kg in male mice, rats, and dogs (fasted for 18 hours prior to administration of diisopropyl methylphosphonate), approximately 90% of the diisopropyl methylphosphonate was absorbed from the gastrointestinal tract. This estimate is based on the small percentage of the label found in the feces in the 2-3-day period after dosing and the 84-97% excreted in the urine (Hart 1976 Ivie 1980). 

Studies of excretion in animals following oral administration of TOCP and tri-para-cresyl phosphate suggest that organophosphate esters found in hydraulic fluids may be extensively absorbed by the gastrointestinal tract (Abou-Donia et al. 1990a, 1990b Kurebayashi et al. 1985 Suwita and Abou-Donia 1990). 

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