ABSTRACT
Keywords................................................................................................................ 274 Abbreviations.......................................................................................................... 274 Abstract................................................................................................................... 274 Background............................................................................................................. 274 Overview.of.Drug.Metabolizing.Enzymes............................................................ 275 Methods.for.Studying.In Vitro.Metabolism:.Enzyme.Sources.............................. 276 Determination.of.Metabolism.in.In Vitro.Systems................................................ 279 High-Throughput.Screening.in.Drug.Metabolism................................................. 281 In Vitro-In Vivo.Scaling.of.an.NCE...................................................................... 281 Induction.of.CYP.Enzymes.................................................................................... 281 Assay.Systems.for.Induction..................................................................................282 Modeling.of.CYP.Enzymes....................................................................................282 Role.of.Animal.Metabolism.Studies.During.Drug.Development.......................... 283 Conclusions............................................................................................................. 283 References............................................................................................................... 283
Drug.metabolism,.cytochrome.P450,.CYP
ADME:.absorption,.distribution,.metabolism,.excretion CYP:.cytochrome.P450 DME:.drug-metabolizing.enzyme HTS:.high-throughput.screening NCE:.new.chemical.entity
Drug.metabolism.profoundly.affects.drug.action.because.almost.all.drugs.are.metabolized.in.the.body,.and.thus.their.concentrations.and.retention.times.are.dependent. on.metabolic.activity..Drug.metabolism.contributes.substantially.to.interindividual. differences.in.drug.response.and.is.also.often.involved.in.drug.interactions,.resulting. in.either.therapeutic.failure.or.adverse.effects..Knowledge.about.the.metabolism.of. a.new.chemical.entity.(NCE).and.its.affinity.to.drug-metabolizing.enzymes.helps.in. the.drug.development.process.by.providing.important.information.for.the.selection. of.a.lead.compound.from.among.a.number.of.substances.equally.effective.in.their. therapeutic.response,.pharmacologically..In.drug.development.protocols,.metabolism. characteristics.should.be.assessed.very.early.during.the.development.process..This. has.been.made.possible.by.the.advances.made.especially.in.in vitro.technologies.used. to.predict.in vivo.drug.metabolism,.kinetic.parameters,.and.interaction.potential.
