Preclinical Pharmacokinetics Industrial Perspective

In parallel to bioanalytical revolution, the drug discovery revolution continues inexorably forward. Today, we not only benefit from revolutionary new medicines that have dramatically improved our quality of life, but we expect even more to come. Compound collections have ballooned through combinatorial library synthesis and advancements in biological science mapped the human genome while we impatiently await the promise of genetically tailored medicines that will treat every ailment. 

The main purposes of this chapter are, first, to introduce the fundamentals of pharmacokinetics derived 

Pharmacokinetics is the science that describes the time course of drug concentration in the body resulting from administration of a certain drug dose. In comparison, pharmacodynamics is the science that describes the relationship of the time course of drug concentration and the drug effects in the body [1]. Therefore, pharmacokinetics can be considered a biomarker of drug exposure as well as a marker of efficacy and safety. Key determinants of the pharmacokinetics of a drug include absorption, distribution, metabolism, and elimination (ADME) [2]. 

Discovering novel therapeutic agents is an increasingly time-consuming and costly process. Most estimates indicate that it takes approximately 10-15 years and more than 800 million to discover and develop a successful drug product [3]. It is well established in the literature that poor drug pharmacokinetics is one of the leading causes of compound failure in preclinical and clinical development [4]. Compounds with poor pharmacokinetic profile tend to have low oral systemic 

Mass Spectrometry Handbook, First Edition. Edited by Mike S. Lee. 

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