ADME
Properties
Optimization of the ADME (Absorption, Distribution,
Metabolism, and Excretion) properties of the drug molecule
is often the most difficult and challenging part of the
whole drug discovery process. The ADME profile will also
have a major impact on the likelihood of success of a drug.
See also the section on Formulation, Solubility
Hints that all is not
well with the pharmacokinetic profile of a drug
candidate.
Dose proportionality issues, increasing dose does not lead
to a corresponding increase in plasma levels :- Absorption
issues
Good plasma levels but little in the brain:- Active efflux
(PGP substrate).
Plasma levels decrease on repeat dosing:- Enzyme induction.
Plasma levels increase when co-administered with another
drug:- Enzyme inhibition.
Duration of action does not match half-life :-Active
metabolites.
Absorption Assays that can be used
to evaluate absorption properties, interpretation and
possible strategies to provide solutions.
Distribution Assays and properties
of molecules effecting plasma protein binding.
Brain Penetration
Assays and
properties of molecules influencing brain penetration
Transporters proteins involved in
transporting molecules/ions into and out of cells
Metabolism Assays, interpretation
of in vitro data, General Strategies for reducing
metabolism.
Excretion (In Progress)
See Also CYP450
Interactions
Updated 6 December 2009
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