In Vitro ADME
Whether you are in the early stages of discovery or preparing to submit an NDA, our comprehensive platform of in vitro services provides you with the quality data you need to predict pharmacokinetics (PK) and pharmacodynamics (PD) in vivo. Offering a comprehensive list of assays, from early discovery to definite regulatory designs, supported by our bioanalytical services unit for method development and validation, our in vitro ADME services are available for both small and large molecule drugs, and can be tailored to fit the specific requirements of your program.
Specific Capabilities: in vitro ADME
Physical Chemistry
- Pharmaceutics: Solubility, pKa, logD, logP
Absorption
- Permeability: Caco-2, MDCK, PAMPA
- Efflux transporters BCRP, P-gp, BSEP, MRP2, MRP3, MRP4 as membrane vesicles
- Transfected and double transfected MDCK II cells (BCRP, P-gp, BCRP±OATP2B1)
Distribution
- Red blood cell partitioning
- Protein binding: Dialysis, ultracentrifugation, etc.
- Tissue binding
Metabolism
- Matrix stability: Tissue, plasma, SGF/SIF, buffer
- Metabolic stability: Microsomes, S9, hepatocytes, CYP phenotyping
- Metabolite ID: Structure determination and quantitation
Drug-drug interaction
- CYP Inhibition/Induction: IC50, reversible inhibition, TDI, KI/Kinact, activity and/or mRNA
- Transporters OAT1, OAT3, OATP1B1, OATP1B3, OCT1, OCT2, PEPT1, 2, MATE1, 2K, NTCP, ASBT as cell-based assays
Assay Automation
- Four liquid handling systems (Tecan, Biomek) for ADME assay automation (latest addition Tecan fluent 1080)
- Rigorous validation and trending of each automated assay.
- Currently automated assays include:
- Permeability assays
- Metabolic stability
- Transporter assays
- Cyp Inhibition
- Dilutions for bioanalytical method development
Learn about our 10mg DMPK Discovery Package
Solution I: We know the target (assume the brain is the target)
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Assay |
Study Design |
Compound Distribution(mg) |
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In vitro ADME |
Phase Ⅰ |
MMS |
Liver microsome stability (CD-1 mouse and Human) |
2.0 |
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PPB |
Plasma protein binding - HTD (CD-1 mouse and Human) |
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BHB |
Brain homogenate binding (CD-1 mouse) |
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MDR1 |
Bidirectional permeability in MDR1-MDCK II cells |
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DDIM |
CYP inhibition for 5-in-1 cocktail substrates |
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KS |
Aqueous solubility (Kinetic) |
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Log D |
LogD measurement at pH 7.4 |
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Phase Ⅱ (Option) |
HMS |
Stability in hepatocytes (CD-1 mouse and Human) |
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Met ID |
In vitro Met ID in liver microsomes (SD rat, Human, Beagle dog, Cyno monkey and CD-1 mouse) |
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In vitro Met ID in hepatocytes (SD rat, Human, Beagle dog, Cyno monkey and CD-1 mouse) |
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PLS |
Stability in plasma (CD-1 mouse and Human) |
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Caco-2 |
Bidirectional permeability in Caco-2 Cells |
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Efflux potential evaluation in Caco-2 Cells |
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TDI |
CYP time dependent inhibition (IC50 shift, 5 CYPs, 6 substrates) |
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pKa |
pKa measurement (spectrometric method) |
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Mouse PK Study |
· 9 male mice (CD-1/C57BL/6), n=3/route · Group 1& Group 2: Single compound administered via 2 routes (IV+PO), 7-8 blood sampling time points up to 24 hours post dosing per animal · Group 3: Brain perfusion, terminal sacrifice, collect brain and CSF · Method development and 48 plasma samples +3 brain samples +3 CSF samples bioanalysis with LC-MS/MS · PK data submission in excel report |
2.0 |
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Mouse PD Study |
· Choose appropriate animal model and the dosage of PD study depends on PK parameters Group 1: 6 males PO (normal) Group 2: 6 males PO (vehicle) Group 3: 6 males PO (positive control) Group 4: 6 males PO, Plasma, CSF and brain (low) Group 5: 6 males PO, Plasma, CSF and brain (middle) Group 6: 6 males PO, Plasma, CSF and brain (high) · PK data submission in excel report |
6.0 |
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Solution II: We don’t know the target
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Assay |
Study Design |
Compound Distribution(mg) |
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In vitro ADME |
Phase Ⅰ |
MMS |
Liver microsome stability (CD-1 mouse, SD rat and Human) |
2.0 |
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PPB |
Plasma protein binding - HTD (CD-1 mouse, SD rat and Human) |
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MDR1 |
Bidirectional permeability in MDR1-MDCK II cells |
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DDIM |
CYP inhibition for 5-in-1 cocktail substrates |
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KS |
Aqueous solubility (Kinetic) |
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Log D |
LogD measurement at pH 7.4 |
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Phase Ⅱ (Option) |
HMS |
Stability in hepatocytes (CD-1 mouse, SD rat and Human) |
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Met ID |
In vitro Met ID in liver microsomes (SD rat, Human, Beagle dog, Cyno monkey and CD-1 mouse) |
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In vitro Met ID in hepatocytes (SD rat, Human, Beagle dog, Cyno monkey and CD-1 mouse) |
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PLS |
Stability in plasma (CD-1 mouse, SD rat and Human) |
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Caco-2 |
Bidirectional permeability in Caco-2 Cells |
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Efflux potential evaluation in Caco-2 Cells |
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TDI |
CYP time dependent inhibition (IC50 shift, 5 CYPs, 6 substrates) |
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pKa |
pKa measurement (spectrometric method) |
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Rodent PK |
Mouse PK study |
· 6 male mice (CD-1/C57BL/6), n=3/route · Group 1& Group 2: Single compound administered via 2 routes (IV+PO), 7-8 blood sampling time points up to 24 hours post dosing per animal · Method development and 45 plasma samples bioanalysis with LC-MS/MS · PK data submission in excel report |
8.0 |
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Rat PK study (Option) |
· 6 male SD rats, n=3/route · Group 1& Group 2: Single compound administered via 2 routes (IV+PO), 7-8 blood sampling time points up to 24 hours post dosing per animal · Method development and 45 plasma samples bioanalysis with LC-MS/MS · PK data submission in excel report |
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End-to-End ADME Solutions
When you engage the Laboratory Testing Division as your testing platform, you can be confident our team of experts will take your compound from start to finish, navigating all of the complexities in between. Our in vitro services span from discovery through definitive ADME, delivering the data-driven support you need to advance your development efforts and reach the ultimate goal of providing therapeutic value for patients.
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Discovery ADME |
IND-Enabling ADME (Early ADME) |
NDA-Enabling ADME (Definitive ADME) |
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Physicochemical Characterization |
X |
X |
X |
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Permeability & Solubility |
X |
X |
X |
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Solution-Phase Stability |
X |
X |
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Metabolism and Clearance |
X |
X |
X |
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CYP Inhibition |
X |
X |
X |
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CYP Induction |
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X |
X |
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Protein Binding (Plasma, Brain or Tissue Homogenate) |
X |
X |
X |
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Blood-Plasma Partition |
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X |
X |
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Transporter Drug-Drug Interactions (inhibition and substrate) |
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X |
X |
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Metabolite Identification and structure elucidation |
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X |
X |
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Enzyme Phenotyping (CYP, UGT, MAO, AO, SULT, etc) |
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X |
X |