Urinary excretion rate calculation

In 1990, urine samples from an accidental laboratory exposure to sulfur mustard were obtained (Jakubowski et al., 2000). The erythematous and vesication areas of the individual were estimated to be less than 5% and 1%, respectively, of the total body surface area. The assay measured both free and conjugated TDG using GC-MS (Jakubowski et al., 1990). The maximum TDG urinary excretion rate was 20 (pg/day on day 3. TDG concentrations of 10 ng/mL or greater were observed in some samples for up to a week after the exposure. A first-order elimination was calculated from days 4 through 10 and found to be 1.2 days. A great deal of intraday variability was noted for the TDG urine concentrations. Attempts were made to estimate the total amount of sulfur mustard on the skin of the patient. The estimate was based on two assumptions (1) that the assay for the free and conjugated TDG represents approximately 5% of the total amount of sulfur mustard related products in the blood, and (2) that the bioavailability factor from skin to blood is 10. A total of 0.243 mg of TDG was recovered over a 2 week period. This would represent 4.86 mg in the blood or 48.6 mg on the skin. 

Metabolites of tea catechins are excreted in bile or urine. In general, small conjugates, such as monosulfates, tend to be excreted in urine, and extensively conjugated metabolites are more likely to be excreted in bile. The total amount of metabolites excreted in urine correlated roughly with maximum plasma concentrations. " The exact half-lives of tea catechins in plasma were calculated to be in the order of 2-3 h, except for EGCG, which is eliminated more slowly. " Relative urinary excretion data were used to estimate the minimal absorption rate and were consistent with the plasma kinetic data for most catechins, but for EGCG that mostly excreted in bile, the urinary excretion rate was very small (0-0.1%), and its absorption was underestimated. The urinary excretion rates of EC and EGC were 18.5 and 11.1%, respectively. The low cumulative excretion of tea catechins in human urine, which was 0-9.8%, suggested that they were extensively metabolized in the human body. 

F values were thus determined directly, k parameters for these molecules were also assessed by monitoring urinary excretion following Intravenous administration of a labelled dose ( ). Typically, k and F values are associated with a standard deviation of 10-15Z (. The experimental results are plotted In Figures 2-10 on each figure, calculated urinary excretion rates are also given... 

Global kinetics, however, allowed calculation of some parameters in normal volunteers, i.e., fractional catabolic rate, rate of synthesis, and mean residence time determined by the mathematical analysis of both plasma decay curves and urinary excretion rates. Such studies demonstrated different metaboUsms for Apo C-I, C-II, and C-III. They may supply essential information on the perturbations observed in pathology. 

When a drug is eliminated by both metabolism and urinary excretion, it is possible to calculate the metabolic clearance rate (MCR) by the difference between TCR and RCR ... 

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 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,... 

In vivo experiments on 4 human volunteers, to whom 0.0026 mg/cm2 of 14C-benzene was applied to forearm skin, indicated that approximately 0.05% of the applied dose was absorbed (Franz 1984). Absorption was rapid, with more than 80% of the total excretion of the absorbed dose occurring in the first 8 hours after application. Calculations were based on urinary excretion data and no correction was made for the amount of benzene that evaporated from the applied site before absorption occurred. In addition, the percentage of absorbed dose excreted in urine that was used in the calculation was based only on data from rhesus monkeys and may not be accurate for humans. In another study, 35-43 cm2 of the forearm was exposed to approximately 0.06 g/cm2 of liquid benzene for 1.25-2 hours (Hanke et al. 1961). The absorption was estimated from the amount of phenol eliminated in the urine. The absorption rate of liquid benzene by the skin (under the conditions of complete saturation) was calculated to be low, approximately 0.4 mg/cm2/hour. The absorption due to vapors in the same experiment was negligible. The results indicate that dermal absorption of liquid benzene is of concern, while dermal absorption from vapor exposure may not be of concern because of the low concentration of benzene in vapor form at the point of contact with the skin. No signs of acute intoxication due to liquid benzene dermally absorbed were noted. These results confirm that benzene can be absorbed through skin. However, non-benzene-derived phenol in the urine was not accounted for. 

Table II shows renal excretion data. Calculated values were obtained from Equations 38, 44, 47, and 52. Here, the rate constants of acetosulfamine and sulfadimethoxine are as well correlated as those of the other compounds for rats and rabbits. This could be expected since the kEx value is directly determined by the proportion of the integrated amount of non-metabolized drug in the total urinary excreted materials whereas the kAc value is derived by assuming that metabolites, other than N-4-acetyl derivatives, are negligible in the urine. For humans, the rate constant of sulfadimethoxine is well correlated while that of acetosulfamine is not. The latter may be excreted by a different mechanism as mentioned.

The mechanisms of salicylate-induced renal lesions are uncertain, but inhibition of medullary prostaglandin synthesis with resultant ischaemia has been proposed (137, 139 ). Further studies have confirmed that aspirin causes acute tubular damage (160, 161). It also inhibits renal tubular gluconeo-genesis (162). Aspirin readily produces typical renal papillary necrosis in rats in doses as low as 200 mg/kg/day and dehydration predisposes to nephrotoxicity (139 , 140 ). In another study, no comparable lesions were produced in rats in a short-term study using daily doses of 24-125 mg/kg. It was claimed that these doses were equivalent to consumption of 8—40 aspirin tablets daily in man (163). However, these calculations were based on comparisons of estimated total salicylate in the body derived from urinary excretion data. Such an approach is quite inappropriate since it does not take into account species differences in the extent or rate of absorption, distribution, protein binding, metabolism and renal medullary concentrations of salicylate. Experimental analgesic nephropathy has been critically reviewed (164 ). 

The mass of endogenous creatinine excreted into the urine, collected over a given time interval (At), is determined. (For each interval, mass creatinine excreted is the product of urinary creatinine concentration times the volume of urine collected.) The mass excreted per rmit time is the rate of creatinine excretion, which is calculated by dividing the mass of creatinine excreted by the time over which it was collected. Next, the mean serum creatinine concentration 0 ) over that interval is calculated from sample determinations this represents the concentration halfway through the interval. In practice, At=24h (1440 min). As (Cs)cr is usually relatively constant, the serum sample is taken at any convenient time. 

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