| Permeability | Drug absorption | |
Caco-2 cells Permeability Assay |
|
Parallel artificial membrane permeability assay (PAMPA) |
| Hepatic excretion | |
Sandwich cultured hepatocytes |
| Plasma protein binding | Protein binding | |
Plasma protein binding assay (Equilibrium dialysis) |
| Drug metabollism | Metabolic stabililty | |
Microsomal stability assay |
|
S9 stability assay |
|
Hepatocyte stability assay |
|
Plasma stability |
|
Species comparison (mouse, rat, dog, monkey, human) |
| Reaction phenotyping | |
Phase I (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, 3A5 etc.) |
|
Phase II (UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 2B15) |
|
Phase I (Non-CYPs, FMO, CES, MAO etc.) |
|
Enzyme systems in the test (Recombinant enzymes, Microsomes, S9, Hepatocytes) |
|
Kinetic studies (Km, Vmax, intrinsic clearance) |
|
Pharmocogenetics study (CYP2C19*10, 2D6*10B, 4F2*3) |
| Met ID | |
Metabolites profiling and Met ID |
| Drug transporters | Transporter substrate identification | |
Uptake transport screening in overexpressing cells or oocytes (OCTs, OATs, OATPs, MATEs) |
|
Efflux transport screening in overexpressing cells (P-gp, BCRP, MRP1, MRP2) |
|
Cryopresesrved hepatocytes uptake |
|
Kinetic studies (Km, Vmax, intrinsic clearance) |
|
Pharmacogenetics study (OCT2 A270S, OATP1B1*15, NTCP*2, MDR1 G2677T/A, BCRP Q141K) |
| Drug-Drug interaction | Metabolizing enzyme inhibition | |
Cytochrome P450 (CYP) inhibition assay (IC50) |
|
UGT inhibition assay (IC50) |
|
Cytochrome P450 Inhibition Ki assay |
| Time-dependent inhibition | |
Cytochrome P450 (CYP) time dependent inhibition (single point) assay |
|
Cytochrome P450 time dependent inhibition (IC50 shift) assay |
|
Cytochrome P450 time dependent inhibition (kinact/KI) assay |
|
GSH conjugate (reactive metabolite) |
| Transporter inhibition | |
P-glycoprotein and BCRP Inhibition assay |
|
BSEP, MRP1, MRP2 Inhibition assay |
|
Uptake transport inhibition in overexpressing cells or oocytes (OCTs, OATs, OATPs, NTCP) |
| Induction | |
mRNA expression level in human hepatocytes (CYPs, UGTs, Transporters) |
|
CYP activity in human hepatocytes |
|
Reporter assay (PXR) |
| In vitro to in vivo Extrapolation | |
IVIVE prediction |
| Preclinical study | Linearity / Bioavailability | |
IV/Oral administration PK |
| Mass balance | |
Radio-labeled compound PK |
| Distribution | |
Tissue distribution (brain, liver, kidney...) |
| Met ID | |
Metabolites profiling and Met ID |
| Billiary /Renal excretion | |
Bile cannulation |
| Bioanalytical services |
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