Faeces elimination

There are very limited data on the kinetics and metabolism of organotins in laboratory mammals. A widespread distribution of organotins throughout body tissues has been observed. Transplacental transfer seems to occur, whereas transfer across the blood-brain barrier is limited, since brain levels are usually low. The only compound for which data are available on metabolites is dibutyltin, which has butyl(3-hydroxybutyl)tin as its major metabolite. Limited information suggests quite rapid metabolism and elimination, with half-lives of several days. Much of an oral dose of dioctyltin was eliminated in the faeces, with the remainder in urine. 

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. 

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. 

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

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. 

It is readily absorbed orally. It is metabolized in the liver and undergoes enterohepatic recirculation. It is eliminated in faeces with a half-life of 5-7 days. Its most common adverse effects are hot flushes. 

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. 

The anthracyclines, apart from valrubicin, are administered intravenously. Doxorubicin is rapidly distributed to tissues and slowly eliminated in faeces and urine with an elimination half-life of several days. Daunorubicin undergoes extensive metabolism in the liver, among others to the active daunorubi-cinol, and is eliminated as inactive products with an elimination half-live of approximately 30 hours. Epimbicin and idambicin have similar kinetic profiles as daunombicin with respectively epirubici-nol and idarubicinol as their major metabolic products. The kinetic behavior of mitoxantrone resembles more that of doxorubicin with a very slow elimination from the body mainly as parent compound or as inactive metabolites. The anthracyclines do not cross the blood-brain barrier. 

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. ... 

Zolpidem is rapidly absorbed and has a quick onset of hypnotic action. Bioavailability is 70 percent following oral administration and the drug demonstrates linear kinetics in the therapeutic dose range. Peak plasma concentration is reached at 0.5 and 3 hours. The elimination half-life is short. It is 92% plasma protein bound and is metabolised in liver to inactive metabolites. It is eliminated in the urine and in the faeces. 

In liver it is extensively biotransformed by oxidation, with less than 5 percent of the dose excreted unchanged in urine. Majority of dose is excreted in urine with up to 15 percent of the dose is eliminated in the faeces. 

Because distribution studies have monitored total radioactivity, our understanding of the distribution of intact di(2-ethylhexyl) phthalate is limited. Chu et al. (1978) studied the metabolism and distribution of mono(2-ethylhexyl) phthalate in rats after oral dosing and found that the intestine contained the highest tissues levels after 24 h. The liver, heart, lung and muscle each contained approximately half the level in the intestine. They also reported that 80% of the I C-dose of mono(2-ethylhexyl) phthalate was eliminated 24 h after oral administration, 72% in the urine and 8% in the faeces. Twenty minutes after the administration of an intravenous dose of [ C]mono(2-ethyl-hexyl) phthalate, Chu et al. (1978) found comparable levels in the liver, kidney and bladder, with other organs containing approximately 10-25% of the level of the liver. 

There are important quantitative differences between species in the routes of elimination of coumarin metabolites. In rats, biliary excretion occurs with an appreciable proportion of the dose excreted in the faeces (Cohen, 1979 Lake, 1999). For example, after a 50-mg/kg bw oral or intraperitoneal dose of coumarin to rats, some 50% was excreted in the bile as unknown metabolites within 24 h (Williams et al., 1965). The urine appears to be the major route of coumarin excretion in Syrian hamsters, rabbits and baboons, but not in marmosets (Kaighen Williams, 1961 Waller Chasseaud, 1981 Lake et al, 1989a, 1990 Lake, 1999). 

The excretion balance and tissue distribution of radiolabelled tris(2,3-dibromo-propyl) phosphate in rats were examined by Lynn et al. (1980, 1982) and Nomeir and Matthews (1983). After intravenous administration of 1.76 mg/rat, Lynn et al. (1980) recovered 57% of the dose in the urine in five days and identified the diester bis(2,3-di-bromopropyl) phosphate as a minor urinary metabolite (7.8% of urinary - C). In further work, Lynn et al. (1982) recovered a total of 86% of the dose in the excreta (58% urine, 9% faeces, 19% as expired 4CO2) with a further 9% in the carcass. Bile-duct-cannulated rats excreted 34% of the dose in the bile in 24 h, 20% being eliminated in the first hour after dosing. No unchanged tris(2,3-dibromopropyl) phosphate was detected in the urine, but dibromopropanol was present in addition to the diester previously reported. On high-performance liquid chromatography, numerous iC peaks remained unidentified. 

Following topical administration of [ 4C]4,4 -methylenediphenyl diisocyanate in acetone to female Wistar rats, 20% of the administered dose was eliminated in the faeces within 24 h, while less than 1% appeared in the urine (Vock Lutz, 1997). 

Plasma peak concentrations are achieved within 2 h and the elimination half-life is about 12 h. Within the clinical dose range, there is high plasma protein binding ( 97%). Celecoxib is metabolized primarily via cytochrome P450 2C9 to three inactive main metabolites. It is excreted in faeces ( 57%) and urine ( 27%) as determined by administration of a single oral dose of radiolabeled drug. Celecoxib is given orally (200-400 mg/day). 

Lornoxicam reaches peak plasma concentrations within 2 to 6 h and shows high degree of binding to plasma protein (99.7%). In contrast to other oxicams, lornoxicam has a short plasma elimination half-life of about 4 h (Olkkola et al., 1994) and is metabolised mainly to the inactive compound 5 -hydroxy-lornoxicam (Dittrich et al., 1990) and excreted in the urine ( 33%) and faeces ( 66%) (Hitzenberger et al., 1990). 

Peak plasma concentration of meclofenamate occur 0.5 to 1 h after oral administration. The binding to plasma proteins is over 99% and the plasma elimination half-life is about 2 to 4 h. Meclofenamate is metabolized by oxidation, hydroxylation, dehalogenation, and glucuronidation. Metabolites are excreted mainly in the urine with about 20 to 30% being excreted in the faeces (Koup et al., 1990). A 3-hydroxymethyl metabolite of meclofenamate has been reported to be active. 

Meloxicam reaches peak plasma concentrations about 8 h after oral dosing. More than 99.5% binds to plasma proteins and it has an elimination half-life of 20 h. Meloxicam is metabolized to four inactive metabolites and excreted in the urine and faeces. 

Peak plasma concentrations are reached within about 2 to 3 h after oral administration. The terminal plasma elimination half-life is between 2 and 5 h. Nimesulide is subject to extensive metabolism. The principal active metabolite is 4-hydroxy-nimesulide. Nimesulide and its metabolites are excreted in the urine ( 70%) and the faeces ( 20%). 

The peak plasma concentration is reached 2 h after oral administration. The degree of binding of phenylbutazone to plasma proteins is 98%. The long elimination half-life of phenylbutazone (mean -70 h) exhibits large interindividual and intraindividual variation. It is metabolized in the liver by oxidation and glucuronidation and excreted in the urine and to a lower degree (-25%) in the faeces (Aarbakke, 1978). Oxyphenbutazone is an active metabolite of phenylbutazone. The metabolic pathway of phenylbutazone is shown in Scheme 72. 

Rofecoxib reaches peak plasma concentrations between 2 to 9 h after oral administration. It is bound 87% to plasma protein and has an elimination half-life of about 17 h. Its main metabolites in the liver are the c/ s-dihydro and trans-dihydro derivatives which are excreted mainly in the urine (72%) with some unchanged drug excreted in the faeces (14%). 

Neotame is reported to have some flavour-enhancing properties, for example, of mint. It is rapidly metabolised by the body, yielding de-esterified neotame and small amounts of methanol. It does not accumulate in the body and is eliminated via the urine and faeces. Owing to its structure, L-phenylalanine is not a metabolite and, therefore, a PKU (phenylketonuria) statement is not required. No ADI has been assigned (The NutraSweet Company, 2003). 

The metabolic fate of Cisobitan is reported by Vessman et al.59. Although the compound is highly lipophilic and nearly water insoluble (solubility 3 jug/ml), it is eliminated primarily via urine and faeces after peroral administration. Analysis of... 

Clearance of cyclosporin A and its metabolites proceeds mainly through excretion of bile into faeces. After an oral dose of [3H]cyclosporin A, only 4-6% of the radioactivity is excreted in urine within 96 h. Intact [3H]cy-closporin A contributes only a small proportion of the excreted radioactivity (0.1-0.2% of the dose). The elimination half-life of cyclosporin A from blood, determined by HPLC, amounts to 15.8 8.4 h. 

Owing to low hydrophilicity only a small part of atenolol is metabolised (about lo of a dose . The drug is also poorly bound to plasma protein (less 5 of the amount in blood).(lo) Mostly of the drug is eliminated, in its unchanged form, by several routes, but prevailing via the kidney.(11) After oral administration atenolol is excreted with urine to the extent of about 4o (12-14), after intravenous administration to the total urinary excretion encompasses 75-loo of the dose (about lo--14 appeared in the form of catabolites).(12,15, 16) Urinary pH variations do not change the extent of excretion with the urine.(1 ) Evidences was put forward to show that atenolol is not eliminated exclusively by glomerular filtration.(11) Atenolol is also excreted with the faeces. After intravenous... 

Elimination is predominantly renal, with about 80% of an oral dose being excreted as urinary metabolites. The remainder is excreted in the faeces and originates primarily from biliary secretion [1],... 

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