Appearance in systemic fluids

1 Appearance in systemic fluids In addition to the method of administering the test substance, the second critical aspect of a technique is the sampling procedure for quantitating the extent and/or rate of absorption. With in vivo methods the least invasive techniques entail the collection of blood, urine, or breath samples for determining the appearance of the absorbed test substance (and its metabolites) in body fluids. Comparing the time course of plasma concentrations or excretory rates in urine or breath after oral administration with the results after intravenous administration may permit quantitation of the extent of absorption of the test substance and the rate constant of this process [20]. This approach is relatively imprecise and may be confounded by numerous factors such as the rsf pass effect, the enterohepatic circulation of the agent, and the status of elimination processes such as hepatic and 

A more direct approach for analyzing absorption characteristics than the sampling of systemic or excreted body fluids entails the sampling of portal blood [24] or the collection of the mesenteric blood draining the sites of absorption of the test substance. Such a procedure requires considerably more complicated surgical techniques than that of sampling systemic blood, urine, or breath. Furthermore, transfusions of blood into the animal may be required. An important advantage of this procedure is the 

In the closed segment procedure, referred to above, the extent of absorption is calculated on the basis of disappearance of the test substance from both the lumen and the intestinal tissue. With the closed segment method, at the end of the absorption period, the entire segment, both intestinal wall and contents, is assayed quantitatively for the amount of the test substance remaining. A disadvantage to this technique when compared with perfusion methods is that sequential samples cannot be taken from a single animal. However, this method is readily used in small animals and can therefore be relatively economical. 

In both the perfusion and the closed segment procedures, equating loss of a fest substance with its absorption requires verification that disappearance does not result as a consequence of metabolism in the intestine. If metabolism of the substance does occur, then assay of the intestine alone is inadequate for a description of its absorption kinetics, xmless the metabolite is poorly absorbed and can be completely recovered in the intestinal samples. 

Additional digestive system safety pharmacology tests include effects of test articles on gastric emptying rate and gastric secretion. Gastric 

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