In Vitro ADME
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A Comprehensive Platform
Whether you are in the early stages of discovery or preparing to submit a New Drug Application (NDA), WuXi AppTec’s DMPK team offers a comprehensive platform of in vitro services that provide you with 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 to predict your compound’s pharmacokinetics (PK) and pharmacodynamics (PD).
Offering a comprehensive range of assays, from efficient screening in early discovery to robust regulatory standard study designs, our in vitro Absorption, Distribution, Metabolism and Excretion (ADME) services are available for both small and large molecule drugs and will be tailored to fit the specific requirements of your program. Our team offers:
- Years of experience with challenging compounds, including highly metabolically stable or highly bound compounds, covalent inhibitors and PROteolysis TArgeting Chimeras (PROTACs)
- Strong bioanalytical capabilities to ensure robust assay development
- Adherence to the most updated guidance on in vitro DDI evaluation
- Validated Caco-2 permeability assay to help you predict human absorption
- Validated Multidrug Resistant (MDR1)-Madin-Darby Canine Kidney (MDCK I) assay to provide you with better in vitro in vivo correlation (IVIVC) for Central Nervous System (CNS) drug development
Specific Capabilities: in vitro ADME
Physical Chemical Properties
Solubility, pKa, LogD and LogP
Permeability
- PAMPA, Caco-2, MDCK II , MDR1-MDCK II, MDCK I, MDR1-MDCK I, BCRP-MDCK II and 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 and non-CYP Enzymes
- Cytochrome P450 (CYP) inhibition (% inhibition or IC50)
- PXR/AXR/CAR Activation and CYP induction (activity and mRNA)
- CYP phenotyping
- UGT, FMO and SULT etc. phenotyping
Assay Automation
- Six liquid handling systems (Tecan®, Hamilton®, Biomek) for ADME assay automation
- Rigorous validation for each automated assay.
End-to-End ADME Solutions
When engaging the WuXi AppTec DMPK team as your partner, you can be confident that our experts will work with you to understand the issues and help you navigate a path to success. Our in vitro services provide the data-driven support you need to design, select and advance your compounds to your next milestone.
| | 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 |