Urinary excretion rate determination

Renal clearance (Cl) of any compound (X) can be determined by comparing the urinary excretion rate of compound X to the plasma concentration of compound X. 

The standards for bioequivalence are similar worldwide, but as a specimen we can use the Code of Federal Regulations, Title 21 (21CFR), parts 320.1-320.63) in the United States. The regulation states that bioequivalence is .. demon-demonstrated if the product s rate and extent of absorption, as determined by comparison of measured parameters, for example concentration of active drug ingredient in the blood, urinary excretion rates, or pharmacological effects, do not indicate a significant difference from the reference material s rate and extent of absorption . 

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. 

To allow estimation of human biotin requirements and evaluation of potential deleterious efiects of marginal degrees of biotin deficiency, indicators of biotin status need to be determined and validated. Several explored directions include serum concentrations and urinary excretion rates of biotin and biotin metabolites, activities of the biotin-dependent decarboxylases in peripheral blood mononuclear cells, and urinary excretion rates of 3-hydroxy-isovaleric acid 3-methylcrotonyl glycine and 2-methylcitric acid. 

No studies were located regarding toxicokinetic data in humans. Limited information is available regarding the toxicokinetic differences among animal species. Rats, mice, mink, and dogs showed rapid absorption, wide distribution, and over 90% urinary excretion of diisopropyl methylphosphonate or its metabolites. However, the rates of absorption and patterns of distribution varied (Hart 1976 Weiss et al. 1994). The mechanism of toxicity is also undetermined. From the limited data available, it is not possible to determine the degree of correlation between humans and animals. 

The main factor in determining whether or not a drug or poison will be excreted via the urinary tract is its lipophilicity. If the material is lipophilic it can be reabsorbed by passive diffusion. The glomerular filtration rate, individual tubule secretory systems, and tubule exchange systems will help to establish excretion rates. Because a molecule s lipophilicity can be pH-dependent the acidity of the urine is extremely important. 

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.

Nephropathy is initially manifested as a persistent urinary excretion of albumin, a decreasing glomerular filtration rate and increasing blood pressure. Once proteinuria occurs, patients have a poor prognosis. The median survival is about 10 years, which is determined by diastolic blood pressure, dietary protein intake and the severity of diabetes exposure. A family history of longevity, however, may be helpful and also regular clinical contact. 

Urinary free cortisol obtained from a 24-hour urine collection is an integrated measure of plasma free cortisol and eliminates the circadian influence on cortisol secretion. Urine free cortisol measurements are therefore considered to be the best screening test for hyperadrenocorticism. The urinary free cortisol excretion rate in normal subjects falls between 20 and 80[lg/day (Figure 51-9), The measurement of urinary 17-hydroxycorticosteroid excretion rates for determining adrenocortical hyperfunction is no longer recommended because of problems with method sensitivity and specificity. 

As mentioned above, metabolic clearance can be predicted making use of appropriate in vitro systems. The urinary excretion can be predicted using the glomerular filtration rate of the freely available (i.e., unbound) compound in combination with the compound s and its metabolite(s) lipophilicity [44], However, we are still lacking appropriate in vitro methods to determine active transport over the tubular epithelial layer [45]. 

Excretion. Contrast media are excreted in both the bile and urine the route that predominates is determined by their chemical structure and route of administration. In general, contrast molecules with an unsubstituted position in the benzene nucleus will be sufficiently lipophilicto bind to the proteins and will be absorbed in peroral administration and excreted in the bile and urine. On the other hand, if the benzene nucleus is fully substituted, the contrast molecules will be highly hydrophilic, will not bind to the proteins, and will be rapidly excreted in the urine. The nonionic contrast media are highly soluble in water and will not be adequately ab-sorbedper 05. Hepatic and urinary excretions of ionic contrast agents and their rates of excretion have been reviewed by Catell (688), Knoefel and Carrasquer (768), McChesney (769), and Sperber and Sperber (749). 

A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. Almost all the urate in plasma is freely filtered across the glomerulus. The concentration of uric acid appearing in the urine is determined by multiple renal tubular transport processes in addition to the filtered load. Evidence favors a four-component model including glomerular filtration, tubular reabsorption, tubular secretion, and postsecretory reabsorption. ... 

The urinary excretion pattern of the 11-oxy-17-OS during the first few days bears more resemblance to that found in adults (Table 10), but again paper chromatography shows other compounds with similar polarity to be present (C6). The rate of excretion of a major unknown substance is given in Table 10, and it will be seen that the urinary content of this and of the known compounds rapidly decline over the first few days. The results shown were determined by scanning paper chromatograms stained with Zimmermann reagent. Identification of the named steroids was not complete and consisted of a comparison of 1 / values in various solvent systems before and after acetylation of the compounds. 

The difficulty in obtaining satisfactory evidence may be due to the fact that thrombosis is a local circulatory problem which will require release of heparin locally for control. Such amounts will not be apparent in gross biochemical tests either as an increase in plasma concentration or a decrease in concentration in tissue. It is probable that heparin will be like other auto-pharmacological agents (e.g. adrenalin, steroids, insulin) in that the amount of heparin in the general circulation at any one time is only a secondary reflection of secretion levels. More important is the determination of rate of urinary excretion of metabolites and still more important the determination of rate of secretion by the glandular tissue (mast cells) itself. 

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