Importance of pharmacokinetic studies

Over the last decade, similar discussions have been going on in the closely related field of pharmacokinetic studies for registration of pharmaceuticals. This is reflected by the number of publications on this topic published in the last decade, of which the most important are discussed here. 

Given the foregoing discussion of some of the unique characteristics of macromolecules that lead to clear differences in their pharmacokinetics compared to those typical of small-molecule drugs, there is a subset of the entire group of bioanalytical assay validation parameters that are of key importance in support of pharmacokinetics of candidate macromolecular therapeutics. Assuming demonstration of accuracy and precision of sufficient quality for the intended application of the assay (e.g., non-GLP discovery support or GLP toxicokinetic support, as discussed above), the most important characteristics of a given assay in support of pharmacokinetic studies are likely to be selectivity, specificity, and reproducibility for analysis of incurred samples. These are all related to the ability of the LBA to detect and quantitate solely, or as closely as possible to solely, the analyte of interest. 

Chapter 9 shows the importance of PLC in the critical field of medical research, with representative examples of the applications to amino acids, carbohydrates, lipids, and pharmacokinetic studies. 

Pharmacokinetics is closely related to pharmacodynamics, which is a recent development of great importance to the design of medicines. The former attempts to model and predict the amount of substance that can be expected at the target site at a certain time after administration. The latter studies the relationship between the amount delivered and the observable effect that follows. In some cases the observable effect can be related directly to the amount of drug delivered at the target site [2]. In many cases, however, this relationship is highly complex and requires extensive modeling and calculation. In this text we will mainly focus on the subject of pharmacokinetics which can be approached from two sides. The first approach is the classical one and is based on so-called compartmental models. It requires certain assumptions which will be explained later on. The second one is non-compartmental and avoids the assumptions of compartmental analysis. 

The main pre-clinical species used for pharmacokinetic studies are the rat, mouse and dog. An examination of the Biosys database for 2000 and 2001 shows that of the abstracted papers, 6334 mapped to the subject heading Pharmacokinetics . Of these, the vast majority (70%) were studies on humans. Studies on rats constituted 14% of the reports, mice 7.5% and dogs 3.4% (Table 6.2). Nonhuman primates can also be important pharmacokinetic models, but ethical and practical considerations severely limit studies in these animals such that, within the same period, they represented less than 0.5% of the abstracted reports on PK. 

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