Drug development
is far from a straightforward endeavor. It starts with the identification of a
pharmaceutically promising substance, the potential of which is further investigated
in near-exhausting physiological analyses. If it is found effective, this does
not necessarily mean that we know all the molecular consequences when
administered. Each patient is an individual, with unique features, which may
mean patient treatment at the level of the individual; so-called personal medicine.
This illustrates the complexity of drug development and discovery. Does it get
any simpler when we consider the physiological and molecular events upon drug
ingestion? A perorally administered drug first of all enters the
gastrointestinal tract where it encounters the biotransformatory activity of
the intestinal microflora. Our knowledge of which compounds finally enter the
blood stream is fragmentary at best, not to mention the interactions of the
drug with the different organs and the resulting organ–organ interplays. And
this is not the only question arising. How do drugs interact with human
physiology? Whether we can simulate drug effects then becomes very important.
Further, how do the organs interact with each other upon the ingestion of a
drug? Can we achieve a whole-body simulation? Or virtual populations? Can we,
and to what extent, treat individuality and gender in drug administration? What
advantages lie behind technologies that can simulate drug action and effect ?
If we can do all this, how can we use these simulations to our advantage in drug
discovery and development? To what are undesired side-effects attributable? What
do we know of drug–drug interactions, drug–drug metabolite interactions, and
their outcomes on organs or on the interplay between different organs? Can we,
by applying novel methodologies, shorten package inserts, even make them superfluous?
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