In Vitro ADME
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A Comprehensive Platform
Whether you’re in the early stages of discovery or preparing to submit a New Drug Application (NDA), WuXi AppTec offers comprehensive in vitro services that give you the quality data needed to understand the disposition and optimization of your New Chemical Entity (NCE). For potential drug candidates, the data and derived modelling has also proven effective in predicting a compound’s pharmacokinetics (PK) and pharmacodynamics (PD).
From efficient screening in early discovery to robust regulatory standard study designs, our in vitro Absorption, Distribution, Metabolism and Excretion (ADME) assays are available for both small- and large-molecule drugs, and tailored to fit the specific requirements of your program.
Our DMPK services include:
- Expertise working with challenging compounds, including highly metabolically stable or highly bound compounds, covalent inhibitors and PROteolysis Targeting Chimeras (PROTACs)
- Strong bioanalytical capabilities, ensuring robust assay development
- Adherence to current guidance on in vitro DDI evaluation
- Validated Caco-2 permeability assay for predicting human absorption
- Validated Multidrug Resistant (MDR1)-Madin-Darby Canine Kidney (MDCK I) assay for improved in vitro in vivo correlation (IVIVC) for Central Nervous System (CNS) drug development
In Vitro ADME Capabilities
Physical Chemical Properties
- Solubility, pKa, LogD & LogP
Permeability
- PAMPA, Caco-2, MDCK II, MDR1-MDCK II, MDCK I, MDR1-MDCK I, BCRP-MDCK II & double-transfected MDCK II cells (BCRP±OATP2B1)
- Efflux transporters BCRP, P-gp, BSEP, MRP2, MRP3 and MRP4 as membrane vesicles
Distribution
- Blood-to-plasma ratio
- Protein binding: Equilibrium dialysis, ultracentrifugation and ultrafiltration
- Tissue binding
Metabolism
- Matrix stability: Tissue, plasma, SGF/SIF and buffer
- Metabolic stability: Microsomes, S9, hepatocytes, cytosol, mitochondria and supersomes
CYP & Non-CYP Enzymes
- Cytochrome P450 (CYP) inhibition (% inhibition or IC50)
- PXR/AXR/CAR Activation & CYP induction (activity and mRNA)
- CYP phenotyping
- UGT, FMO, SULT, etc. phenotyping
Assay Automation
- Six liquid-handling systems (Tecan®, Hamilton®, Biomek) for ADME assay automation
- Rigorous automated-assay validation
End-to-End ADME Solutions
Our in vitro services provide the data-driven support you need to design, select and advance your compounds to the next milestone. You can be confident our experts will collaborate with you to understand the issues specific to your project, and help you find – and navigate – a path to success.
| | Discovery ADME | IND-Enabling ADME (Early ADME) | NDA-Enabling ADME (Definitive ADME) |
|---|---|---|---|
| Physicochemical Characterization | X | X | X |
| Permeability and Solubility | X | X | X |
| Solution-Phase Stability | X | X | X |
| Metabolism and Clearance | X | X | X |
| CYP Inhibition | X | X | X |
| CYP Induction | X | X | |
| Protein Binding (Plasma, Brain or Tissue Homogenate) | X | X | X |
| Blood-Plasma Partition | X | X | |
| Transporter Drug-Drug Interactions (inhibition and substrate) | X | X | |
| Metabolite Identification and structure elucidation | X | X | |
| Enzyme Phenotyping (CYP, UGT, MAO, AO, SULT, etc) | X | X |