Abstract: The key to clinical success of a compound
is often curtailed due to inadequate safety,
pharmacokinetics or efficacy. To aid in success of the
discovery program, accurate pharmacokinetic and
metabolic data of an in-vitro biological screening is
essential. This review highlights the various in-vitro
and in-silico models used to predict absorption and
metabolism providing a wealth of information to make
decisions. Absorption systems include excised tissue,
stripped and unstripped mucosal sheets, cultured cells
such as Caco-2, HT-29, and MDCK, parallel artificial
membrane permeation assay, mucosal cell membrane
vesicles. In-vitro metabolism models give information on
metabolite stability, metabolite profile, metabolite
identification, interspecies comparisons, toxicology
species selection, cytochrome induction/inhibition,
drug/drug interaction and Phase II enzyme studies. Liver
being the major organ for drug metabolism, human liver
slices, expressed enzymes, liver microsomes and isolated
hepatocytes are used for prediction of metabolism. In
silico models have received considerable attention in
the development and design of clinical trials. This
article also focuses on the various in silico models
available for determining ADME. Prediction of absorption
is done using iDEA, metabolism involves COMPACT, META
and METEOR. Computer systems available for the
prediction of toxicity are DEREK and Hazard Expert.
These computer programs have formed the basis for
comparing and contrasting their functionality and
utility in predicting ADME. Expert use of these
prediction tools could lead to lower failure rates in
drug development and decrease the cost and time involved
in success of drug approval.
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