Early drug metabolism phase

Compound optimization in early- and late-phase drug discovery is covered, emphasizing physicochemical properties, in vitro absorption, metabolism and in vivo animal pharmacokinetic methodologies. 

Some oxidative (Phase I) drug-metabolizing enzymes are already present in the human foetal liver as early as 12 weeks after conception. Others progressively appear as foetal age advances, although... 

He took over the responsibility for the complete Drug Metabolism and Pharmacokinetics Department in Frankfurt in 2000. His activities ranged from in-silico approaches at very early stages of the value chain, in-vitro studies, and in vivo animal studies up to Phase I, II and III clinical studies. The whole scope of these activities... 

What is the underlying cause for these interspecies differences For equal doses, differences in plasma AUC values simply indicate differences in total body clearance. Renal and metabolic elimination processes are the major contributors to total body clearance. When allometric scaling is used as described in Chapter 30, renal clearance tends to exhibit only small differences across species, whereas there are many examples of interspecies differences in metabolism. Further, across many drug categories, metabolism is quantitatively more important than is renal elimination. Therefore, more emphasis on inter species differences in drug metabolism could improve Phase I studies. The next two sections provide specific examples of the impact of monitoring metabolism during early human studies. 

In silico approaches to predict drug metabolism are of particular interest to the pharmaceutical industry as having the potential to impact the early drug discovery process as well as in the candidate selection phase. The identification of metabolic soft spots in a new chemical entity could help improve the hepatic... 

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