Recent advances in high throughput screening for ADME properties.
With the increase in the numbers of molecules synthesized in a typical drug discovery program, as well as the large amount of information utilized in the selection of a drug candidate, there is a need for a plethora of drug metabolism and pharmacokinetic (DMPK) information to be regularly generated in discovery. Over the past decade, many in vitro, and even in vivo, DMPK screens have been developed and routinely deployed to generate this information in support of drug discovery efforts. In the past few years, newer methods, or adaptations to methods, have been published, and this review attempts to summarize these advances. In particular, advances have been reported for experimental approaches to metabolic clearance, CYP inhibition, in vivo exposure, and distribution, as well as in silico determinations of absorption, distribution, metabolism, and excretion (ADME) properties. Bioanalytical approaches aimed at optimizing analyte method development, sample preparation, and analyte detection, have also been reported. Future advances will further improve the ability to make decisions on molecules earlier in drug discovery.
Carlson
Timothy J
TJ
Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
Fisher
Michael B
MB
D000818:Animals; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000639:trends; D006801:Humans; D008099:Liver / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D010539:Permeability; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
D054852:Small Molecule Libraries; D003577:Cytochrome P-450 Enzyme System