Metabolite excretion rates

Determined from sum of indene metabolite excretion rates. 

Thermochemical Optimization of Microbial Biomass-Production and Metabolite-Excretion Rates... 

In this paper, the Mlchaells-Menten reaction mechanism will be modified to eliminate these and other shortfalls. The modified reaction mechanism will then be used to explore the Influence of substrate concentration on the optimum temperature of blomass-productlon and metabolite-excretion rates. The Influence of dilution rate will also be examined. The scope of analysis will still be confined to processes whose rates saturate In substrate concentration. 

At this point, it would appear that one can account for most of the observed effects of temperature and dilution rate on the macro-coefficients by simply assuming temperature dependencies such as those shown in Figure 3 for the micro-coefficients in eqtiatlons (20) - (27). These equations with the parameter values specified in Figure 3 will now be used to analyze the thermal sensitivity of the net biomass production and metabolite excretion rates. 

But if it were set at the optimum temperature for the net biomass production rate, the metabolite excretion rate would be only slightly suboptlmal (Figure 9). 

In contrast, the optimum operating temperature for the metabolite excretion rate is strongly affected by both dilution rate and substrate concentration. As substrate concentration... 

Figure 3.18 Scheme of one-compartment intravenous bolus model of drug eliminated by both urinary excretion and metabolism. X,mass (amount) of drug in the blood/body at time, t X , mass of unchanged drug in the urine at time t Xm, mass of metabolite in the blood/body at time f X u, mass of metabolite in the urine at time t ff , first-order renal excretion rate constant (time ) K , first-order metabolite formation rate constant (time ) Kmu, first-order metabolite excretion rate constant (time ). 

Hehnersson, J and Basu S (2001) Fj-isoprostane and prostaglandin Fj metabolite excretion rate and day to day variation in healthy humans. Frost Leak Ess Fatty Acids, 65,99-102. 

Cortisol Metabolites Excretion Rates of females and males... 

Figure 4 Cortisol (a) and androgen (b) metabolite excretion rates (corrected for body size) from childhood to adulthood. Since no significant sex differences have been observed, data have been combined.

Differences among individuals can partially explain the differences in the before workshift and end of workshift levels of trichloroethylene and its metabolites. Increased respiration rate during a workday, induced by physical workload, has been shown to affect levels of unchanged trichloroethylene more than its metabolites, while the amount of body fat influences the levels of the solvent and its metabolites in breath, blood, and urine samples before workshift exposure (Sato 1993). Additionally, liver function affects measurements of exhaled solvent at the end of workshift increased metabolism of trichloroethylene will tend to decrease the amount exhaled after a workshift. Increased renal function would affect levels of TCA and trichloroethanol in blood before a workshift in the same way, but it probably would not affect urine values between the begiiming and the end of the workshift because of the slow excretion rate of TCA. 

Excretion of free atrazine in urine is consistent with the pattern of exposure, with maximal excretion rates at the end of the workshift and a rapid decrease after cessation of exposure. This pattern suggests that atrazine does not accumulate in the body (Catenacci et al., 1990). Atrazine metabolism gives rise to bi-dealkylated (80%), deisopropylated (10%), and deethylated (8%) metabolites, which are eliminated in urine over a period slightly longer... 

LSD is consumed (p.g) and the low excretion rates reported for LSD (1%) and its metabolites (1.2% for nor-LSD and 2-25% for O-H-LSD) in the peer-reviewed literature [40-42], Moreover, these compounds were rarely present in the investigated wastewaters and O-H-LSD, the LSD metabolite excreted at the highest rate, was absent in the surface waters. All this reasoning leads to suspect the existence of a potential interference in the analyses. 

The consumption indicator is the metabolic byproduct excreted at the highest rate. It may be a metabolite, as it is the case for cocaine (BE) and heroin (MOR), or the drug itself, as it is the case of amphetamine-like compounds. THC, the most psychoactive cannabinoid of the cannabis herb, is highly metabolized before excretion, thus, the consumption indicator selected (THC-COOH) presents an excretion rate of 0.6%. Despite the fact that OH-THC presents a slightly higher excretion rate (2%), this analyte was not selected to back calculate cannabis use due... 

Portmann and co-workers then studied the kinetic pathways in man for hydroxynalidixic acid, the active primary metabolite.(26) The rate constants for glucuronide formation, oxidation to the dicarboxylic acid and excretion of hydroxynalidixic acid were calculated. Essentially total absorption of hydroxynalidixic acid was found in every case. Good agreement between experimental and theoretical plasma levels, based on the first order rate approximations used for the model, was found. Again, the disappearance rate constant, kdoi was found to be very similar for each subject, although the individual excretion and metabolic rate constants varied widely. The disappearance rate constant, k was defined as the sum of the excretion rate constant, kg j and the metabolic rate constants to the glucuronide and dicarboxylic acid, kM-j and kgj, respectively. 

Large, generalist marine grazers such as fishes and urchins attempt to choose foods that maximize nutritional input (e.g., protein, lipids, and carbohydrate) (Mattson 1980 Choat and Clements 1998) and minimize intake of secondary metabolites (Hay 1991). The untested assumption underlying these optimal foraging decisions is that detoxification and excretion rates are a constraint on toxin intake and thus drive feeding choice (Freeland and Janzen 1974). However, we have virtually no information on such constraints in marine herbivores, because it requires an understanding of the metabolic fate of secondary metabolites. 

White rats given a single dose of radiolabeled disulfoton intraperitoneally eliminated the metabolites phosphoric acid (4.1 %), DEP (61.2%), and DETP (24.8%) in urine as a percentage of excretory metabolites 10-12 hours after exposure (Bull 1965). Approximately 24 and 48 hours after exposure 14.1% and 28.6%, respectively, of the administered dose was excreted in the urine. Excretion rates for disulfoton and its metabolites were not determined. Mice eliminated 30--60% of the radiolabeled intraperitoneal dose of disulfoton in the urine and 2-3% in the feces within 96 hours of exposure (March et al. 1957). 

Absorption, Distribution, Metabolism, and Excretion. No studies were located regarding the absorption, distribution, metabolism, and excretion of disulfoton by humans or animals after inhalation or dermal exposure. Limited data exist regarding the absorption, distribution, and excretion after oral exposure to disulfoton. Data on levels of disulfoton and metabolites excreted in urine and expired air suggest that some almost complete absorption of an administered dose of disulfoton over 3-10 days (Lee et al. 1985 Puhl and Fredrickson 1975). The data are limited regarding the relative rate and extent of absorption. Animal data suggest that disulfoton and/or its metabolites are rapidly distributed to the liver, kidney, fat, skin, muscle, and brain, with peak levels occurring within 6 hours (Puhl and Fredrickson 1975). Elimination of disulfoton and metabolites occurs primarily in the urine, with >90% excreted in the urine in 3-10 days (Lee et al. 1985 Puhl and Fredrickson 1975). 

Biological monitoring for exposure to phenol is possible by measuring blood or urine levels of the parent compound. However, it should be noted that phenol and metabolites of phenol may also come from other sources. For example, phenol is a metabolite of benzene and of protein metabolism. Urine samples taken from male workers employed in the distillation of high-temperature phenolic fractions of tar revealed a phenol excretion rate of 4.20 mg/hour compared to a control rate of 0.53 mg/hour for non-exposed workers (Bieniek 1994). Samples were taken 4 hours into the workers workday, but the worker exposure levels were not reported. 

Comparative Toxicokinetics. The metabolism and excretion of orally administered phenol in 18 animal species have been compared to metabolism and excretion in humans (Capel et al. 1972). The rat was the most similar to the human with respect to the fraction of administered dose excreted in urine in 24 hours (95%) and the number and relative abundance of the 4 principal metabolites excreted in urine (sulfate and glucuronide conjugates of phenol and 1,4-dihydroxybenzene). The rat excreted a larger fraction of the orally administered dose than the guinea pig or the rabbit (Capel et al. 1972) and appears to be the least susceptible of the three species to respiratory, cardiovascular, hepatic, renal, and neurological effects of inhaled phenol (Deichmann et al. 1944). More rapid metabolism and excretion of absorbed phenol may account for the lower sensitivity of the rat to systemic effects of phenol. More information on the relative rates of metabolism of phenol in various species is needed to identify the most appropriate animal model for studying potential health effects in humans. 

The primary endpoint of the toxicokinetic studies is the concentration-time prohle of the substance in plasma/blood and other biological fluids as well as in tissues. The excretion rate over time and the amount of metabolites in urine and bile are further possible primary endpoints of kinetic studies, sometimes providing information on the mass balance of the compound. From the primary data, clearance and half-life can be derived by several methods. From the excretion rate over time and from cumulative urinary excretion data and plasma/blood concentration measured during the sampling period, renal clearance can be calculated. The same is the case for the bUiary excretion. 

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. 

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. 

Oral doses of piperazine are readily absorbed with peak plasma levels 2 hours after dosing. The drug is excreted in the urine with an elimination half-life of about 3 hours. However large interindividual differences were found for the excretion rate of both unchanged drug and its metabolites. 

A number of benzimidazoles exist as prodrugs their anthelminthic activity is due to the fact that they are metabolized in the animal body to the biologically active benzimidazole carbamate nucleus. Due to their relatively slower excretion rates, the newer insoluble benzimidazoles have fairly long withdrawal periods for edible tissues and milk in contrast to the less effective and more rapidly excreted thiabendazole analogues. Strict compliance with withdrawal periods is always necessary because of the potentially toxic and teratogenic effects of some of the benzimidazoles and their metabolites. 

Bioavailability. Bioavailability has become an important part of the QA effort to prove that the product maintains its strength, safety, purity, and efficacy during its shelf life. Since bioavailability was introduced, the scientist has not been satisfied with chemical equivalence between batches of product, and this expanded the QA effort. The study of bioavailability makes it necessary to know how the body s physiology and biochemistry are affected by the drug molecule s availability within it. The drug s concentration in the body fluids, its ability to bind protein, its metabolic rate, its ability to present the active metabolite at the needed site of action, and the body s excretion rate are the tools used to measure the drug s bioavailability. 

The widespread detection of phthalate metabolites in human urine has produced questions about public-health risks, especially with regard to antiandrogen effects that can influence male gonadal development (Gray et al. 2000 Parks et al. 2000). The extrapolation from urinary biomonitoring results to exposure and risk assessment has been facilitated by calculations that convert urinary metabolite concentrations to intake dose of the parent phthalate (Koo et al. 2002 Koch et al. 2003 Kohn et al. 2000 David 2000). The parent diester phthalates are rapidly and completely metabolized to the monoester metabolites, which are rapidly cleared by the kidney. Those features allow one to assume that the daily excretion rate of metabolite is equal to the daily intake rate of the parent chemical. Furthermore,... 

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