Metabolic rate constant determination

Biological. A bacterial culture isolated from the Oconee River in North Georgia degraded 3-nitroaniline to the intermediate 4-nitrocatechol (Paris and Wolfe, 1987). A Pseudomonasstrain P6, isolated from a Matapeake silt loam, did not grow on 3-nitroaniline as the sole source of carbon. However, in the presence of 4-nitroaniline, all of the applied 3-nitroaniline metabolized completely to carbon dioxide (Zeyer and Kearney, 1983). In the presence of suspended natural populations from unpolluted aquatic systems, the second-order microbial transformation rate constant determined in the laboratory was reported to be 4.6 + 0.1 x 10 L/organism-h (Steen, 1991). 

Whereas compartmental models are abstract mathematical representations of an animal or a human body, in the form of a certain number of boxes, PBPK models describe the behavior of xenobiotics on the basis of the actual anatomy, physiology, and biochemistry of human beings and animals. Being realistically modeled on how the body functions, PBPK models take into consideration the complex relationships that exist between critical biological and physicochemical determinants such as blood flow, ventilation rates, metabolic rate constants, tissue solubilities, and binding to proteins (e.g., albumin and glycoproteins) or other macromolecules (e.g., DNA and hemoglobin). 

Kim C, Manning RO, Brown RP, Bruckner JV. Use of the vial equilibration technique for determination of metabolic rate constants for dichloromethane. Toxicol Appl Pharmacol 1996 139 243-51. 

Several TRK-850 derivatives were synthesized based on the general strategies mentioned above, and their metabolic stabilities were evaluated in the presence of human liver microsomes. Metabolic rates were determined by incubating the compounds with human liver microsomal enzymes and then quantifying the remaining parent peak by HPLC analysis. The data were expressed as the elimination rate constant (Kel) and the relative metabolic rate, or the /C , [ of the compound compared with the /C, [ of TRK-850 (ATF, ratio). 

Nomeir and Hajjar 1987 Poonawalla and Korte 1964 Sasaki et al. 1992 Tashiro and Matsumura 1978). Further studies could be designed to estimate metabolic rate constants and to determine the levels at which saturation of specific pathways occurs with different routes of exposure. 

Heiss, W. D., Pawlik, G., Herholz, K. etal. Regional kinetic constants and cerebral metabolic rate for glucose in normal human volunteers determined by dynamic positron... 

The uptake, distribution, and metabolism of 1,3-DNB were studied in hydroponically grown mature soybean plants (Me Farlane et al. 1987a). Initial uptake rate constants of 1,3-DNB by soybean plants determined by measuring either chemical loss from solution, C concentration in plants, or root... 

When a compound is administered by a route other than intravenously, the plasma level profile will be different, as there will be an absorption phase, and so the profile will be a composite picture of absorption in addition to distribution and elimination (Fig. 3.26). Just as first-order elimination is defined by a rate constant, so also is absorption kab. This can be determined from the profile by the method of residuals. Thus, the straight portion of the semilog plot of plasma level against time is extrapolated to the y axis. Then each of the actual plasma level points, which deviate from this during the absorptive phase, are subtracted from the equivalent time point on the extrapolated line. The differences are then plotted, and a straight line should result. The slope of this line can be used to calculate the absorption rate constant kab (Fig. 3.26). The volume of distribution should not really be determined from the plasma level after oral administration (or other routes except intravenous) as the administered dose may not be the same as the absorbed dose. This may be because of first-pass metabolism (see above), or incomplete absorption, and will be apparent from a comparison of the plasma... 

Kinetic constants of pentachloroethane metabolism have been determined in male Fischer 344 rats exposed to the vapour phase at a concentration of 2895 mg/ni for 6 h and then placed in exhaled breath chambers. The maximum metabolic rate was... 

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 basal metabolic rate (BMR) is the rate of use of the body s energy stores. The BMR is determined while at rest after an overnight fast. Generally, the BMR Is determined soon after awakening and 14 hours after the last meal. The BMR is fairly constant over the course of a day as illustrated in Figure 5.21, These data are from a study of a human subject. Respiratory gas samples were taken at various intervals and used for O and CO analyses. The results of the analyses were used to calculate the rate of O2 consumption, the RQ, and the metabolic rate at the indicated times. The results demonstrate that the BMR during the first hour of rest was about 190 kj/hr... 

The model simulations were in close agreement with the observed results from the distribution and metabolism studies. Physiological processes that were highlighted by the results and the discrepancies that did occur include the probable active transport into the brain (versus passive diffusion) of a methyl-mercury-cysteine complex, the bidirectional transport of methylmercury between the gut lumen and gut tissue as a more important determinant of methylmercury fecal excretion than biliary secretion, the importance for the determination of methylmercury half-life in rats of the recycling of mercury from ingested hair, and the need for better estimates of the rate constants for the demethylation of methylmercury in order to adapt the model to other species. 

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