| |
항목 |
요소기술 |
| In vitro metabolism |
Metabolic stability |
Metabolic stability in microsomes, hepatocytes, plasma, blood |
| Subcellular metabolism |
Hepatocytes, S9 fraction, cytosol, microsomes, intestine |
| Metabolic route and kinetics |
Reaction phenotyping and kinetics of Phase I (CYPs) and Phase II (UGT) enzymes |
| Interspecies comparative metabolism |
Monkey, dog, hamster, mouse, rabbit, rat |
| Metabolite Identification |
Metabolite structure ID, toxic metabolite ID |
| In vitro transport |
Permeability test |
Permeability in Caco-2, MDCK, LLC-PK1 cells
Cryopreserved hepatocytes uptake
Biliary excretion in sandwich cultured hepatocytes
|
| Transport system and kinetics |
Uptake screening test in Xenopus oocytes
Efflux screening test in MDCK-MDR1, MRPs, BCRP
|
| Pharmacogenetics study |
Transport activity in wild type and variant transporters
|
| Drug-drug interaction |
Inhibition |
Screening of inhibitory potential of CYPs, UGTs, transporters
Estimation of IC50 (Ki) value
|
| Mechanism-based inhibition |
IC50 shift assay, reversibility assay
Estimation of KI and kinact value
|
| Induction |
Reporter assay
mRNA expression level in hepatocytes
Phenotyping assay using specific substrates
|
| In vivo PK (preclinical) |
Mass balance |
Mass balance study using radioactive or non-radioactive compounds
|
| Absorption |
Estimation of bioavailability
|
| Distribution |
Tissue distribution (brain, liver, kidney etc)
Blood partitioning, Protein binding
|
| Metabolic profiling |
Metabolites profiling and Met ID
|
| Excretion |
Renal excretion, biliary excretion, enterohepatic circulation
|
| In vivo PK (human) |
Translational Research |
In vitro to in vivo extrapolation (SimCYP) |
| Interspecies Pharmacokinetic Scaling |
| Consultation of decision making for further clinical development |
| Phase 0 study |
Microdosing study |
| Phase I study |
First in human study |
| Absolute bioavailability |
| Drug-drug interaction potential study (cocktail study) |
| Genotype based ADME study |
| Special population (Gender, nephropathy, hepatic failure, Elderly) |
| Bridging study |
