Faeces, excretion

Dark urine occurs in obstructive jaundice because the water-soluble conjugated bilirubin cannot be excreted through the faeces. Excretion from the body is compensated for by increased kidney elimination, and hence the urine is a darker colour than normal. 

Disposition in the Body. Readily absorbed after oral administration. Eliminated mainly in the faeces excretion may be delayed due to enterohepatic circulation. Small amounts are excreted in the urine as the glucuronide conjugate. 

After dosing the mice are observed and the responses scored either as the number showing a purgative effect (quantal effect) or as the number of wet faeces excreted per mouse (graded effect) and potency estimates with their limits of error calculated by the methods given on page 841. 

The number of wet faeces excreted by the mice, either singly or in pairs, is recorded after not less than twelve hours. 

Excretion of the drug and/or its metabolites takes place primarily in the kidney, though some drugs also show considerable excretion via the bile/faeces. Again, it is important to study the rates of excretion of the drug or its metabolites, and to verify that there is no associated kidney damage. 

Perminks et al. (1987) reported that 80% of a single oral dose of dioctyltin dichloride at 2 mg/kg body weight was excreted in the faeces within 2 days. After 3 days, excretion of radioactivity followed first-order kinetics, with a half-life of 8.9 days. After intravenous administration, 66% of the radioactivity was excreted in the faeces, and a half-life value of 8.3 days was obtained, roughly similar to that of oral administration. Percentages of radioactivity excreted in the urine were 11% and 22% following intravenous and oral dosing, respectively. 

The sulphonamides show a considerable variation in the extent of their absorption into the bloodstream. Sulphadimidine and sulphadiazine are examples of rapidly absorbed ones, whereas succinylsulphathiazone and phthalylsulphathiazole are poorly absorbed and are excreted unchanged in the faeces. 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

Faeces from colonised cows may contain from 102 to 107 colony-forming units (CFU) of Salmonella cells per gram of faeces. Particularly calves and heifers colonised with E. coli 0157 H7 may shed the bacteria at levels ranging from 102 to 105 CFU g 1 (Himathongham el al., 1999). Furthermore, calves younger than four months are the main domestic animals that excrete pathogenic protozoa like Giardia and Cryptosporidia. 

In mice and hamsters, dioxin is excreted with urine, in the rest of animals - with faeces. 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

The main route of excretion is via the faeces (biliary excretion), urine and breast-milk. Excretion through breast-milk results in transfer to breastfed infants, who therefore are highly exposed. There is also transfer across the placenta, thus causing fetal exposure. Perinatal exposure is a major concern with regard to human health effects, even at present background exposure levels. 

The major part of absorbed mercuric mercury is excreted in urine and faeces in about equal parts in rat [49] and man [2, 50]. Since absorption rates from the lung or gastrointestinal tract do not vary greatly from one animal species... 

Bacterial action in the large gut converts the conjugated bilirubin into bilinogens and then to yellow-brown coloured bilins which finally leave the body through in the faeces (as stercobilin) and urine (as urobilin). A small proportion of the bilin produced in the gut is passively reabsorbed into the portal system and re-excreted as the blood flows through the liver. 

Additionally, the incomplete oxidation of fuel generates weak organic acid anions. Furthermore, there is loss of base in the faeces each day which, in effect, leaves the body with an excess of protons to be excreted. In total, about 70 milliequivalents (mEq) of acid require excretion each day. Note mEq is used to quantify the acid load because this takes account of the valency of the ion 1 mmol of sulfate, S04, for example, is 2 mEq of negative charge, requiring 2 mEq of protons for neutralization, but for monovalent ions, such as protons or bicarbonate, 1 mEq= 1 mmol. ... 

After either oral or intravenous administration of [ Cjondansetron to rats the majority (about 80 %) of the radioactive dose is voided in the faeces, the remainder of the dose being excreted in the urine. In the dog, faecal elimination accounts for about half of the dose and is independent of the route of administration. Evidence from animals with cannulated bile-ducts indicates that the major route of excretion is via the bile. In both species, less than 5 % of the dose is excreted unchanged in urine, suggesting that extensive metabolism of ondansetron occurs. 

Drugs Drugs that lower the blood levels of cholesterol are frequently used as part of the treatment these include (i) Oral bile acid binding exchange resins. Resins such as cholestyramine are effective because, when taken by mouth, they prevent the reabsorption of bile acids in the lower small intestine, so that they are excreted in the faeces. Since bile acids are formed in the liver from cholesterol, synthesis of more acids requires more cholesterol uptake by the liver from the blood, which occurs via LDL-cholesterol, so that the concentration of the latter is decreased. 

Excretion via faeces is a minor route of elimination, accounting for less than 10% of the administered dose [113,126],... 

Excretion of the intact drug, and its metabolites, into urine and faeces. 

The cumulative excretion of P840 at 48 hours post-injection was found to be 65 21 % of the injected dose in the urine and 4 1 % in the faeces. Thus,... 

The study should provide unique information on the plasma-concentration profiles of parent drug and metabolite. The rates and extended excretion in urine, faeces and, if appropriate, expired air can be defined. 

Sulfasalazine is absorbed in the proximal intestine and is then excreted unchanged in the bile. In consequence most of orally administred sulfasalzine reaches the colon as such. It is then split by the intestinal flora into its components sulfapyridine, a sulfonamide antimicrobial agent, and 5-aminosalicylic acid (5-ASA). It has been proven that in inflammatory bowel disease 5-ASA is responsible for the beneficial effects while the sulpha component only contributes to the adverse reaction profile. Although some 5-ASA is absorbed and excreted in urine with a half-life of 0.5-1.5 hours, most is eliminated unchanged in the faeces. Sulfapyridine is to a major extend reabsorbed, metabolized in the liver and excreted in the urine with a half-life, depending on the acetylator phenotype, between 5 and 15 hours. 

Differences in clinical effectiveness are partly due to differences in absorption, distribution and excretion of the individual drugs. In general tetracyclines are absorbed irregularly from the gastrointestinal tract and part of the dose remains in the gut and is excreted in the faeces. However this part is able to modify the intestinal flora. Absorption of the more lipophilic tetracyclines, doxycycline and minocycline is higher and can reach 90-100%. The absorption is located in the upper small intestine and is better in the absence of food. Absorption is impaired by chelation with divalent cations. In blood 40-80% of tetracyclines is protein bound. Minocycline reaches very high concentrations in tears and saliva. Tetracyclines are excreted unchanged, in both the urine by passive filtration and in the feces. Tetracyclines are concentrated in the bile via an active... 

It is slowly absorbed orally with peak plasma levels about 4 hours after dosing. Its protein binding is about 75%. It is metabolized in the liver to its tri-azine metabolite, the active compound cycloguanil, with an elimination half-life of on average 16 hours, however, with a wide interindividual variation. It is excreted in urine and faeces as unchanged drug and metabolites. 

It is poorly absorbed from the gastrointestinal tract and is therefore mainly useful for treatment of luminal intestinal infections. It is mainly excreted unchanged in faeces and not more than 15% of the dose is excreted in the urine, either as unchanged drug or in the form of metabolites. 

Niclosamide is a salicylamide derivative. Its mechanism of action could be based on inhibition of oxidative phosphorylation or on its ATPase stimulating action. The scolices and segments, but not segments of the ova, are rapidly killed. Niclosamide is minimally absorbed from the gastrointestinal tract and excreted, mostly unchanged, in the faeces. It is generally well tolerated with occasional gastrointestinal disturbances. Skin eruptions have been reported. 

Absorbed fluoride that is not deposited in calcified tissue is excreted. The primary pathway for fluoride excretion is via the kidneys and urine to a lesser extent, fluoride is also excreted in the faeces, sweat and saliva. 

Certain drugs that are secreted by the liver into the bile and then to small intestine are not eliminated out through the faeces, so that the drugs will re-enter the blood that perfuses the intestine and again carried to the liver (repeatedly reabsorbed from the intestine and re-excreted in the bile) and thereby prolongs the action by the so called enterohepatic circulation. ... 

Morphine orally is less effective and absorption is very slow. It has variable and high first pass metabolism when given by subcutaneous route, its analgesic effect starts within 10 minutes which persists for 4 to 5 hours and by IV route, it produces immediate action. In plasma, it binds to plasma proteins (approx. 30%). In liver it is metabolized by conjugation to glucuronic acid to form active and inactive products, which are excreted in urine. It is also excreted though bile and in the faeces. 

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