Page - (000084) - in Biomedical Chemistry: Current Trends and Developments

Vss − apparent volume of distribution at steady state. 2.1.1 Introduction The first decade of the 21st century was a challenging period for the pharmaceutical industries focused on drug research. Several changes in technology and market dynamics have occurred over the last years and they inexorably revolutionized the drug discovery and development (DDD) process. The tremendous progress in biomedical knowledge and the completion of the human genome sequencing project have accelerated the discovery of the molecular basis of human diseases and have allowed the identification of important new biological therapeutic targets. In addition, the synergistic interaction between rational drug design, recombinant biotechnology and combinatorial chemistry prompted a fast increment of the number of new chemical entities (NCEs) with molecular characteristics propitious to interact with specific biological targets (Ohlmeyer, 2010). Despite this exponential increase in the number of NCEs, pharmaceutical industry is suffering from a lack of productivity considering the number of new drugs that have successfully reached the market (Keserü, 2009). According to recent news, it is estimated that only one in ten drug candidates that enter the clinical development phase will reach the market and the success rate for drugs to be approved considering all the therapeutic areas is only 11% (Tamimi, 2009). The current climate of downward pressure on healthcare costs combined with the need of expensive technologies and greater information about drugs under development prompted pharmaceutical companies to develop paradigm-shifting strategies and tactics in order to cut drug development costs, fill the depleting product pipelines and reverse the trend of dropping productivity. A well-succeeded front- loading approach consisted on selecting, in the early drug discovery stage, the drug candidates that are not only pharmacologically active but also those having desirable pharmacokinetic properties. It is particularly disheartening when the in vitro potency is achieved, but the