Preclinical development pharmacokinetics applications

In dmg discovery, preliminary PK studies are usually conducted in rodents to evaluate the extent of dmg exposure in vivo. This is commonly followed by PK studies in larger animals such as dog or monkey to better characterize the PK profile of the compound and to support safety studies. Pharmacokinetic scaling (also called allometry) is a discipline that is used to predict human PK profiles using preclinical data and is widely used in predicting the dmg human half-life, dose, and extent of absorption. Accurate prediction of a human PK profile is imperative to minimize dmg failure in development due to poor PK attributes. A detailed description of methods in predicting human PK is beyond the scope of this chapter but can be found in many excellent reviews (Obach et al., 1997 Miners et al., 2004 Poggesi, 2004 Raunio et al., 2004 Thomas et al., 2006 Hurst et al., 2007). A more in-depth discussion of various PK concepts and their applications can be found in various references (Gibaldi and Perrier, 1982 Rowland and Tozer, 1995 Hurst et al., 2007). 

Fig. 1.4 Examples of the application of pharmacokinetic/pharmacodynamic (PK/PD) concepts in preclinical and clinical drug development (from [10]).

In addition to these qualitative studies, quantitative bioanalysis, e.g., in preclinical and clinical studies to provide pharmacokinetic and pharmacodynamic data, is an essential part of drug development. Quantitative bioanalysis is the most important application area of LC-MS, in terms of number of instruments applied and the number of analyses performed. Fast, high-throughput, and routine quantitative analysis by LC-MS also demands fast and automated sample pretreatment strategies and advanced data-processing software. 

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