Elimination minor routes

Renal clearance of cotinine is much less than the glomerular filtration rate (Benowitz et al. 2008b). Since cotinine is not appreciably protein bound, this indicates extensive tnbnlar reabsorption. Renal clearance of cotinine can be enhanced by np to 50% with extreme urinary acidification. Cotinine excretion is less influenced by urinary pH than nicotine becanse it is less basic and, therefore, is primarily in the unionized form within the physiological pH range. As is the case for nicotine, the rate of excretion of cotinine is influenced by urinary flow rate. Renal excretion of cotinine is a minor route of elimination, averaging about 12% of total clearance. In contrast, 100% of nicotine Ai -oxide and 63% of 3 -hydroxycotinine are excreted unchanged in the urine (Benowitz and Jacob 2001 Park et al. 1993). 

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

Excretion - Penicillins are excreted largely unchanged in the urine by glomerular filtration and active tubular secretion. Nonrenal elimination includes hepatic inactivation and excretion in bile this is only a minor route for all penicillins except nafcillin and oxacillin. Excretion by renal tubular secretion can be delayed by coadministration of probenecid. Elimination half-life of most penicillins is short (no... 

Metabolism/Excretion- Metabolism is a minor route of elimination. The mean elimination half-life of lamivudine ranges from 5 to 7 hours. The majority of the dose is eliminated in the urine as unchanged drug, with about 5% excreted as the metabolite within 12 hours of dose administration. 

A-Nitrosomorpholine and A-nitrosodiethanolamine are both converted in vivo to A-nitroso-A-2-hydroxyethylglycine, which is excreted in rodent urine. The recovery of A-nitroso-A-2-hydroxyethylglycine in 24-h urine was lower in rats (8%) than in mice or hamsters (11-14%) dosed intraperitoneally with A-nitrosodiethanolamine (5 mg/kg bw), which was also found in urine of all the species (Bonfanti et al, 1986). Biliary excretion (a minor route of elimination) and enterohepatic recycling of A-nitrosodiethanolamine and its metabolite A-nitroso-A-2-hydroxyethylglycine has been shown in rats after intravenous administration of 5 mg/kg bw A-nitrosodi-ethanolamine (Bonfanti et al, 1985). 

The route of entry for chemicals into the body differs in different exposure situations. In the industrial setting, inhalation is the major route of entry. The transdermal route is also quite important, but oral ingestion is a relatively minor route. Consequently, preventive measures are largely designed to eliminate absorption by inhalation or by topical contact. Atmospheric pollutants gain entry by inhalation, whereas for pollutants of water and soil, oral ingestion is the principal route of exposure for humans. 

The AUC increases in a dose dependent manner for 200 to 1600 mg single doses [21], Individual enantiomers show similar half-lives [40]. Following radiolabeled etodolac administration, 69% to 76% of the dose was recovered in urine over 7 days. Urine and feces together accounted for 80% to 92% of dose [15]. Biliary excretion is a minor route for the elimination of etodolac [40]. 

Pharmacokinetics Sildenafil is rapidly absorbed after oral administration, and peak plasma levels are achieved within one hour. Bioavailability is about 40 percent of the oral dose. Sildenafil enters tissues, and has an apparent volume of distribution of 1.5 L/kg. Both sildenafil and its major N-desmethylated metabolite are > 95 percent bound to plasma proteins. Both CYP3A4 (major route) and CYP2C9 (minor route) are responsible for the metabolism of sildenafil. The major metabolite, N-desmethyl sildenafil, is approximately 50 percent as potent as sildenafil in inhibiting PDE5. The major route of elimination for sildenafil and its metabolites is via the bile. Clearance is decreased in older individuals free plasma concentrations are 40 percent higher in healthy volunteers > 65 years old. Severe renal impairment (< 30 mL/min) increases the AUC (see p. 7) by two-fold. Similarly, cirrhosis of the liver also significantly increases the AUC. 

The metabolism and elimination of the trans-isomer was more rapid than those of the cis-isomer. The elimination from the liver is biphasic with an initial rapid phase of 3 days and a slower phase with a half-life of 120 to 13 0 days. The liver is the major organ for the accumulation and storage, which has been found mainly as the unchanged parent compounds. The major route of elimination in different species after oral administration is via the feces. The urine is a very minor route of elimination (Watt et al, 2005). 

Hair is an unexpected and only minor route of elimination for certain chemicals, especially metals. However, the presence of metals in hair has been used as a practical means of monitoring exposure to such chemicals. 

In a study with rats, TBBPA was readily absorbed from the gastrointestinal tract, metabolized in the liver and excreted via the bile to the gut. Of the dose administered to the rats, 90% was excreted in the feces as parent TBBPA. Three glucoronide conjugates of TBBPA were identified in the feces but only accounted for a small amount of the administered dose. Urine was a minor route for excretion of TBBPA. The half-life of TBBPA in rats was estimated to be less than 3 days with the longest half-lives in fat and testes. The shortest half-lives were in liver and kidneys. In a study of occupationally exposed Swedish workers, the half-life for elimination from the serum was 2.2 days indicating a rapid elimination from the body. 

I be to xico kinetics of PBO has also been studied in the goat and hen following daily oral administration for 5 days at a dose level of 10 or 100 mg kg diet. In Ihe goal the (Jose was excreted mainly in the urine (79-1 and 72.6%, respectively) with the remainder being found in the faeces. Milk was a minor route of elimination, accounting for less than 1% of the total dose (Selim, I995aj. 

C-H bond fission and the production of ethynyl radicals. Butadiyne and vinyl acetate are formed when the T -shaped ethyne dimer is irradiated at 193 nm in argon or xenon. The dynamics of the photodissociation of propyne and allene have been studied. The H2 elimination from propyne is a minor route for propyne dissociation and the major path identified in this study is loss of the alkyne hydrogen. A study of the photodissociation dynamics of allene and propyne has been reported and this work has demonstrated that allene gives rise to a propargyl radical while propyne yields the propynyl radical. Other research has examined the photodissociation of propyne and allene by irradiation at 193 nm. ... 

Humans eliminate ingested 1,1,1-trichloroethane in their exhaled breath (Stewart and Andrews 1966), but no studies were located that quantified excretion rates or the extent of excretion. The pattern of elimination is expected to be similar to that of inhaled 1,1,1-trichloroethane (i.e., exhalation of unchanged 1,1,1 -trichloroethane should be the predominant route of excretion exhalation of CO2 and urinary excretion of other metabolites are minor routes). This pattern has been observed in animals after inhalation (see Section 2.3.4.1) and oral exposure (Mitoma et al. 1985 Reitz et al. 

The pathway of plutonium dissolved in natural water, from a source such as a nuclear facility, to man, may be quite complicated. During the transport, the plutonium atoms encounter dissolved and particulate inorganic and organic matter, as well as minerals in rocks, sediment and soil, and living organisms which may metabolize the plutonium. Figure 1 depicts some of the more essential routes for plutonium between the point of emission and the plutonium consuming man. The overall effect of these pathways is that plutonium is slowly eliminated from the water, so that only a minor fraction of it reaches man. An example of this is that of the 4.2 tonnes of plutonium deposited on the earth after... 

Renal excretion is the most important endosulfan elimination route in humans and animals. Biliary excretion has also been demonstrated to be important in animals. Estimated elimination half-lives ranged between approximately 1 and 7 days in adult humans and animals. Endosulfan can also be eliminated via the breast milk in lactating women and animals, although this is probably a relatively minor elimination route. No studies were located regarding known or suspected differences between children and adults with respect to endosulfan excretion. 

The excretion of chloroform and its metabolites is understood, based on human and animal data derived from oral and inhalation studies (Brown et al. 1974a Corley et al. 1990 Fry et al. 1972 Taylor et al. 1974). The major route of chloroform elimination is pulmonary, but minor pathways are through enterohepatic circulation, urine, and feces as parent compound or metabolites. There are no human or animal data regarding excretion of dermally applied chloroform. 

Absorption of fenbendazole is slow in ruminants but more rapid in monogastric animals. Maximum concentrations in blood are achieved at about 8 h in rats and rabbits, 24 h in dogs, and 2-3 days in sheep. Elimination of fenbendazole is predominantly by the fecal route. The metabolic pathway of fenbendazole is similar in rats, rabbits, dogs, sheep, cattle, goats, and chickens. It is rapidly metabolized to fenbendazole sulfoxide (oxfendazole), fenbendazole sulfone, fenbendazole 2-aminosulfone, and other minor metabolites detected in plasma. 

After a single oral administration of 0.4 mg radiolabeled moxidectin/kg bw to horses, a mean peak serum concentration of 0.134 ppm moxidectin equivalents was attained at 6 h postdose (63). Oral availability was estimated at 40%, while the terminal elimination half-life was approximately 80 h. Within 168 h, 77% of the total radioactivity was excreted mostly by Ure fecal route. In feces, the parent drug represented approximately 70% of the fecal radioactivity, whereas a fraction of 0.28-3.45% was due to four minor metabolites resulting from oxidation mainly on Ci4, C24, and/or C28 positions. 

The metabolism and kinetics of cyclohexanone were studied in a group of volunteers (four men and four women) during and after 8-h exposures to 101, 207 and 406 mg/m- . After exposure to 207 mg/m- , the metabolic yields of urinary cyclohexanol, 1,2- and 1,4-cyclohexanediol and their glucuronide conjugates were 1%, 39% and 18%, respectively. The elimination half-times (Aj of the 1,2- and 1,4-diols, respectively, were 16 h and 18 h. Consequently, after repeated exposure over five days, there was no cumulation of urinary cyclohexanol, whereas there was cumulative excretion of the diols. The permeation rate of cyclohexanone liquid through the skin was 37-69 nig/cm per hour, indicating that occupational exposure by this route is of minor importance (Mraz et al., 1994). 

Table 5 summarizes the stereochemical information available for reactions which are assumed to follow the addition-elimination route. Unfortunately, the reliability of the data is not the same for all the systems. Earlier work, where minor products were neglected and proper control experiments were not performed, is subject to some uncertainties. For example, when 100% of one isomer was reported, this generally means that only one product was isolated. Recent data, obtained with more sensitive and less destructive methods, such as NMR, are much more reliable. 

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