Route of excretion

In order to achieve the desired fiber properties, the two monomers were copolymerized so the final product was a block copolymer of the ABA type, where A was pure polyglycoHde and B, a random copolymer of mostly poly (trimethylene carbonate). The selected composition was about 30—40% poly (trimethylene carbonate). This suture reportedly has exceUent flexibiHty and superior in vivo tensile strength retention compared to polyglycoHde. It has been absorbed without adverse reaction ia about seven months (43). MetaboHsm studies show that the route of excretion for the trimethylene carbonate moiety is somewhat different from the glycolate moiety. Most of the glycolate is excreted by urine whereas most of the carbonate is excreted by expired CO2 and uriae. 

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

In intact cell systems or vivo, the primary products of a-hydroxylation, 22. have not been detected. The principal urinary metabolites of NNN resulting from a-hydroxylation are keto acid 21 from 2 -hydroxyl at ion and hydroxy acid 21 from 5 -hydroxylation. Trace amounts of 7 y 21> H ve also been detected as urinary metabolites (34). The interrelationships of these metabolites as shown in Figure 2 have been confirmed by administration of each metabolite to F-344 rats (37). The other metabolites which are routinely observed in the urine are NNN-1-N-oxide U1 and 5-(3-pyridyl)-2-pyrrolidinone [norcotinine, ]. The p-hydroxy derivatives 2. 1 were also detected in the urine of NNN treated rats, but at less than 0.1% of the dose (36). An HPLC trace of the urinary metabolites of NNN is shown in Figure 3. Urine is the major route of excretion (80-90% of the dose) of NNN and its metabolites in the F-344 rat in contrast to NPYR which appears primarily as CO2 (70%) after a dose of 16 mg/kg (17). This is because the major urinary metabolite of NNN, hydroxy acid 21> fs not metabolized further, in contrast to 4-hy-droxybutyric acid [2, Figure 1] which is converted to CO2. In addition, a significant portion of NNN is excreted as NNN-l-N-oxide U ], a pathway not open to NPYR. 

Excretion is the process by which a substance leaves the body. The most common ways are via the kidneys and via the gut. Renal excretion is favored by water-soluble compounds that can be filtered (passively by the glomeruli) or secreted (actively by the tubuli) and that are collected into urine. Fecal excretion is followed by more lipid substances that are excreted from the liver into the bile, which is collected in the gut and passed out by the feces. Other routes of excretion are available through the skin and the lungs. 

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. 

The main rout of excretion of the drug and its metabolites is the kidney with a half-life of 9-18 h in human. In contrast to human, animal models have a lower elimination half-life ranging from 0.6-9 h [78]. The elimination half-life of valproic acid and some metabolites was found to be much longer in the neonates (40-50 h) than adult subjects (9-18 h) [78,81]. One study reported no difference between the elimination half-life between elderly and young subjects (15.4 and 13.0 h, respectively) while other found an increase in for older patients (14.9 versus 7.2 h for young patients) [78,90], Insignificant amounts of valproic acid are found in breast milk, approximately 3% of maternal drug levels [84]. 

The predominant route of excretion in rats is via urine (Gut et al. 1985 Tardif et al. 1987 Young et al. 1977). In rats exposed to 5 ppm of 1- C-acrylonitrile for 6 hours, 68% of the absorbed radioactivity was excreted in the urine within 220 hours, with 3.9% in the feces, 6.1% in expired air as CO2, and 18% of the radioactivity being retained in the body tissues. Following exposure to a higher concentration (100 ppm), a larger fraction of the dose was recovered in urine (82%) and a smaller fraction (2.6%) was retained in the body (Young et al. 1977), indicating that urinary excretion is dose-dependent. Percent fecal excretion was similar at both doses. 

Following oral exposure, the major route of excretion of acrylonitrile in rats is via the urine, either as thiocyanate or as other products of conjugation. Within the first 24 hours of a single oral dose, 40% to 60% was recovered in the urine (Ahmed et al. 1983). Farooqui and Ahmed (1982) reported that 10 days after the administration of a single dose, 61 % of the dose had been accounted for in the urine, 3% in feces and 13% in the expired air. Approximately 25% was retained in the body covalently bound to tissues (see Section 2.3.3). 

The answer is e. (Hardman, pp 16-17.) The amounts of drugs that are excreted in milk are small compared with those that are excreted by other routes, but drugs in milk may have significant, undesired pharmacologic effects on breast-fed infants. The principal route of excretion of the... 

Other routes of excretion are the skin (by means of sweat), hair, and nails. These routes are usually minor compared to the excretion processes of the kidneys, liver, and lungs. 

The blood levels following oral and intravenous doses are very low in all animal species. This, most likely, is due to the marked affinity of the drug for various tissues and the rapid hepatic extraction of the absorbed fraction. The main route of excretion is the bile. Less than 5 % of the dose are recovered in the urine of intact animals after oral or intravenous administration. 

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. 

Hirom [71,72] demonstrated more than three decades ago that the route of excretion of xenobiotics is dependent upon MW by testing up to 75 compounds in rat, guinea-pigs, and rabbits. Lower MW compounds (< 350) were mainly eliminated in the urine (>90%). As MW increased from 350 to 450, a sharp increase in the fraction of compound eliminated in the bile occurred, and for MW > 450, compounds were eliminated 50-100% in the bile in all three species. Smith [73] correlated the log of free metabolic and renal clearance (ml/min/kg) with log D, and found a similar relationship. Metabolic clearance increases with increasing log D, while renal clearance decreases with increasing log D. 

Excretion. Excretion encompasses the process by which chemicals or their metabolites are transported out of the body. There are three possible major routes of excretion, and a handful of minor ones. The major routes of excretion for chemicals, and in particular their metabolites, are as follows. 

The bile contained the greatest amount of llfC-labeled metabolites (Table III), indicating that bile is an important reservoir and route of excretion for metabolites in fish (17). No [llfC]-molinate was detected in bile however, several polar metabolites were present. Six metabolites were revealed by TLC using solvent systems (g), (h), and (i). HMI constituted 3.16% of the total bile radiocarbon based on TLC cochromatography with an authentic standard in the same solvent system. 

Table V contains data for two model substances, p-aminohippurate (PAH) and phenol red. Consideration of the highest values in this table tells you where the major portions of the substances appear. For example, urine and bile show the largest concentrations of PAH and phenol red. Both compounds appear in significant concentrations in the kidney while the values in muscle, brain and cerebrospinal fluid (CSF) are invariably lower than the values seen in plasma. The values in parentheses (Table V) are percent of the administered dose in a given tissue or fluid compartment. They add to the previous information by revealing the overall importance of a particular compartment in the disposition of a substance. For example, while the hepatic concentrations of PAH and phenol red at 4 hrs. are only about 2-fold those of plasma, the large size of the shark liver relative to its body weight, typically about 10%, leads to the appearance of 30-40% of these substances in the liver. The relative handling of these compounds by the urinary and biliary system is obvious from considering the percentage figures. Thus in 24 hours phenol red is about equally distributed in the bile and urine (38 vs 31%) the urinary route is the dominant route of excretion of PAH, i.e., 56 vs 2%.

Excretion is the process of eliminating drugs from the body. They may be excreted as metabolites or as unchanged drug. As mentioned above, compounds that are polar and water soluble are more readily eliminated. The major routes of excretion are renal, biliary/fecal, lactational, and pulmonary. 

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. 

Some minor routes of excretion exist sweat, hair, saliva, semen, milk. While these routes out of the body do not count for much as excretory processes, excretion of some chemicals into milk can be important because it constitutes an exposure pathway for infants, if the milk is from their mothers, and for many people if it is from dairy cattle. Many fat-soluble chemicals follow this pathway out of the body, dissolved in the fatty portion of the milk. Excretion of chemicals through milk is common enough to prompt considerable attention from toxicologists. 

Excretion relates to the physical loss of the parent substance and/or its metabolite(s). The principal routes of excretion are via the urine, bile (feces), and exhaled air. 

The main routes of excretion for a substance as well as for its metabohtes are in the urine and bile (feces). For some substances, exhalation is also an important excretion route. In addition, excretion may also take place via biological fluids such as sahva, sweat, and nulk. Although the amounts excreted by these routes are relatively small, the presence of a substance in these fluids, particularly breast milk, may be the underlying cause of toxic effects. 

For volatile substances and metabolites, exhaled air is an important route of excretion. Substances that are excreted in the urine tend to be water-soluble and of low molecular weight (below 300 in the rat). Substances that are excreted in the bile tend to have higher molecular weights. In the... 

Walton et al. (2001a) examined data for compounds eliminated by the cytochrome P450 isoenzymes CYP1A2 in humans. Absorption, bioavailabihty, and route of excretion were generally similar between humans and the test species for each of the substances (caffeine, paraxanthine, theobromine, and theophylline). However, interspecies differences in the route of metabolism, and the enzymes involved in this process, were identified. The magnitude of difference in the internal dose, between species, showed that values for the mouse (10.6) and rat (5.4) exceeded the fourfold default factor for toxicokinetics, whereas the rabbit (2.6) and the dog (1.6) were below this value. 

No studies were located regarding excretion following oral exposure to 1,3,5-TNB in animals. Following administration of a single oral dose of C-1,3-DNB to rabbits and rats, radioactivity accounting for more than 80% and 63% of the dose, respectively, was excreted in urine, indicating that the main route of excretion is via the urine (Nystrom and Rickert 1987 Parke 1961). Elimination of 1,3-DNB metabolites in urine was rapid and occurred within 48 hours. The major urinary metabolites in rabbits were 2,4-diaminophenol, 1,3-phenylenediamine, and 1,3-nitroaniline (Parke 1961). 

Data on the toxicokinetics of 2-hexanone, as described in this section, were derived from studies using 2-hexanone with purity of 97% or more. As discussed below, absorption of this compound has been demonstrated in humans, dogs, and rats after administration via inhalation, oral, or dermal exposure. Very little information is available on distribution. A metabolic pathway has been proposed based on the metabolites of 2-hexanone identified in the blood of guinea pigs and rats after intraperitoneal and oral administration, respectively. Expired breath and urine appear to be the main routes of excretion for 2-hexanone and its metabolites. 

Limited excretion data are available in humans receiving 2-hexanone via inhalation, oral, and dermal exposure, in dogs via inhalation exposure, and in rats via oral exposure (DiVincenzo et al. 1977, 1978). However, human data on excretion of 2-hexanone via feces are not available, and the available information in dogs concerns excretion via exhaled breath only. In these and any other studies, information on all routes of excretion would help to evaluate the potential for 2-hexanone clearance in the exposed species. Excretion data in rats receiving 2-hexanone via inhalation and dermal application and in other species receiving 2-hexanone via all three routes would be useful for comparison with the human data and to assess the comparative risks of exposure by each route. In addition, information on excretion rates in each species via each route would be helpful in understanding how long 2-hexanone and its metabolites may persist in the body. 

Metabolism by the P450 system results in steady-state peak levels of a major active metabolite (desmethylazelastine), which are 20% to 50% of azelastine levels. The elimination half-life of the metabolite is predicted to be 54 hours. The major route of excretion is via feces. ... 

Pharmacokinetics Venlafaxine is well absorbed (at least 92%) and extensively metabolized in the liver. ODV is the only major active metabolite. Renal elimination of venlafaxine and its metabolites is the primary route of excretion. Venlafaxine ER provides a slower rate of absorption but the same extent of absorption compared with the immediate-release tablet. 

Pharmacokinetics Following oral administration, approximately 55% of the dose can be recovered from the urine. Pergolide is approximately 90% bound to plasma proteins. The major route of excretion is via the kidney. 

Excretion - After oral dosing of two 333 mg acamprosate tablets, the terminal half-life ranges from approximately 20 to 33 hours. The major route of excretion is via the kidneys as acamprosate. 

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