Rate of excretion method

The information necessary for the urinary analysis, empioying either ARE or rate of excretion method, is presented in nine columns in the table. 

Rate of excretion method drug exclusively removed in unchanged form by renal excretion... 

The release of steroids such as progesterone from films of PCL and its copolymers with lactic acid has been shown to be rapid (Fig. 10) and to exhibit the expected (time)l/2 kinetics when corrected for the contribution of an aqueous boundary layer (68). The kinetics were consistent with phase separation of the steroid in the polymer and a Fickian diffusion process. The release rates, reflecting the permeability coefficient, depended on the method of film preparation and were greater with compression molded films than solution cast films. In vivo release rates from films implanted in rabbits was very rapid, being essentially identical to the rate of excretion of a bolus injection of progesterone, i. e., the rate of excretion rather than the rate of release from the polymer was rate determining. 

The apparent rate of excretion was slower after dermal exposure than after oral administration, probably due to slower absorption of the 2,4,5-T ester from the skin than 2,4,5-T acid from the gut. This is in agreement with observations made by Feldmann and Maibach for 2,4-D and other pesticides applied to the forearm of human volunteers (13). Calculations by Ramsey et al. using three methods showed that 97% of the 2,4,5-T absorbed by forest workers would be excreted in urine within 7 days following dermal exposure under typical field conditions (16). 

Numerous methods have been used to increase the rate of excretion of poisons from the body. Of these, only diuresis, multiple-dose activated charcoal, and hemodialysis are useful occasionally. These approaches should be considered only if the risks of the procedure are significantly outweighed by the expected benefits or if the recovery of... 

The most accurate assessments of internal dose can be made when the distribution and total body content of an incorporated radionuclide can be determined reliably by direct in vivo counting of emissions from the body. Nevertheless, biokinetic modelling of retention and biophysical modelling of energy deposition may still be needed to calculate the intake and the committed effective dose, so direct methods can also depend on the interpretation of rates of excretion, which often vary markedly over time and between individuals. 

Description of Method. Creatine is an organic acid found in muscle tissue that supplies energy for muscle contractions. One of its metabolic products is creatinine, which is excreted in urine. Because the concentration of creatinine in urine and serum is an important indication of renal function, rapid methods for its analysis are clinically important. In this method the rate of reaction between creatinine and picrate in an alkaline medium is used to determine the concentration of creatinine in urine. Under the conditions of the analysis, the reaction is first-order in picrate, creatinine, and hydroxide. 

The realization of sensitive bioanalytical methods for measuring dmg and metaboUte concentrations in plasma and other biological fluids (see Automatic INSTRUMENTATION BlosENSORs) and the development of biocompatible polymers that can be tailor made with a wide range of predictable physical properties (see Prosthetic and biomedical devices) have revolutionized the development of pharmaceuticals (qv). Such bioanalytical techniques permit the characterization of pharmacokinetics, ie, the fate of a dmg in the plasma and body as a function of time. The pharmacokinetics of a dmg encompass absorption from the physiological site, distribution to the various compartments of the body, metaboHsm (if any), and excretion from the body (ADME). Clearance is the rate of removal of a dmg from the body and is the sum of all rates of clearance including metaboHsm, elimination, and excretion. 

In principle, isotope dilution could be used to measure the rate of production of water or carbon dioxide by measuring the rate at which the administered " C02 or was diluted. In practice, however, there are difficulties. In the case of water, the amount produced is small compared with the mass of body water, so that the changes in the content of isotope would be too small to measure accurately. The problem with carbon dioxide measurements is the need to take frequent samples because carbon dioxide is rapidly excreted. Two methods have been developed that overcome these problems (see Elia Livesey 1992). 

Very few methods are available for determining the level of 1,3-DNB and its metabolites in human blood and urine (for more information see Chapters). Because 1,3-DNB is rapidly absorbed, metabolized, and excreted, measurement of blood levels of this substance or its metabolites is limited to exposures of a very large magnitude and that occur within a few hours of the time at which the blood sample is obtained. Results from an in vitro study in rat hepatocytes and microsomes show that the relative rate of conversion of 1,3-DNB to nitroaniline is 7 and 12 minutes, respectively (Cossum and Rickert 1985). This would make it difficult to accurately determine the level of 1,3-DNB in the blood and use it as a marker of exposure. 

No studies on body burden reduction methods were located. The state of definitive knowledge of white phosphorus metabolism is too limited to permit extensive speculation on methods for reducing body burden. However, it is possible that increasing selective excretion of phosphate may increase the rate of inorganic conversion of white phosphorus to phosphate (this conversion is described in detail in Section 2.3). Since phosphate is a naturally occurring component of the blood s buffering system, this would effectively deactivate the phosphorus. No methods for selectively increasing phosphate excretion were located. 

As described in several chapters of the present book [1,7], the application of pharmacokinetic (PK) and pharmacodynamic (PD) methods is widely accepted in the pharmaceutical industry. A PK model typically predicts the availability of a drug in the blood and interstitial spaces at different times after the drug has been administered. The model is used to determine characteristic parameters of the absorption, distribution, metabolism, and excretion processes from experimentally observed time courses, or the model follows the rates of formation and removal of various metabolites. PD models describe the effects of the drug (and its metabolites) as a function of time, again based on statistical fits to experimental results. 

The GC/MS procedures for methamphetamine are described in Table 4. The papers published in Japanese - have corresponding reports in English. - - Methamphetamine was detected and determined by mass fragmentography in rat hair after administration of the substance. Nine methods also detected the metabolite amphetamine or amphetamine alone. Suzuki et al. determined methamphetamine also in nail, sweat and saliva. The workup (EX after acid or alkaline hydrolysis) and derivatization technique (methanol-trifluoroacetic acid [TEA]) is rather uniform in most procedures. Nakahara et al. ° used methoxyphenamine excretion into beard hair to discuss several washing procedures. Alkaline or methanolic extraction are used with one exception. Derivatization is mainly made by fluorinated anhydrides. A review ° gives details on analytical procedures, incorporation rates of amphetamines from blood to hair, and relationship between drug history and drug distribution in hair. 

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