Formulations, Routes, and Dosage Designs

In pivotal studies, the actual blood levels of active moiety that are achieved will be determined so that correlations to later clinical studies can be made. 

The formulations that are developed and used for preclinical studies are sometimes specific for the test species to be employed, but their development always starts with consideration of the route of exposure that is to be used clinically and, if possible, in accordance with a specified regimen of treatment (mirroring the intended clinical protocol, as much as possible). One aspect of both nonclinical and clinical formulation and testing which presents an important but often overlooked aspect of pharmaceutical safety assessment is the special field of excipients. These will be considered at the end of this chapter 

As presented in Table 13.1 there are at least 26 potential routes of administration, of which 10 are commonly used in safety assessment and, therefore, are addressed here. 

There are three primary sets of reasons why differences in formulations and the route of administration are critical in determining the effect of an agent of the biological system. These are (1) local effects, (2) absorption and distribution, and (3) metabolism. 

Local Effects. Local effects are those that are peculiar to the first area or region of the body to which a test material gains entry or that it contacts. For the 

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