Prediction of pharmacokinetic properties using experimental approaches during early drug discovery

There has been a significant increase in the number of compounds synthesize d in early drug-discovery programs with the advances in combinatorial chemi stry and high-throughput biological screening efforts. Various in silico, i n vitro and in situ approaches have been described in literature that achie ve higher throughput pharmacokinetic screening. In silico methodologies hav e mainly attempted to quantify the prospects of oral absorption of compound s based upon their physico-chemical properties. There is a greater availabi lity of in vitro and in situ approaches to screen compounds for intestinal permeability (as a surrogate for absorption) and metabolic stability (as a surrogate for clearance). More recent modifications of the in vitro and in situ approaches to assess the potential of absorption and metabolism have e nabled a higher throughput and an ability to correlate better with in vivo pharmacokinetics of compounds.