in vitro ADME
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Expert in vitro ADME Testing Services
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 modeling has also proven effective in predicting a compound’s pharmacokinetics (PK) and pharmacodynamics (PD).
A Global Platform for Your ADME Needs
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:
- Comprehensive assay systems for drug discovery and development
- Full range of in vitro assays to cover FDA, EMA and NMPA requirements
- Fast turnaround time with liquid handing robots to run automated ADME assays
- Strong non-GLP bioanalytical capabilities, ensuring robust assay development
- Expertise working with challenging compounds, highly metabolically stable or highly bound compounds, covalent inhibitors and new modalities, including proteolysis-targeting chimeras (PROTACs), oligonucleotides, and antibody-conjugated drugs (ADC)
- Adherence to current guidance on in vitro DDI evaluation
Our in vitro ADME Capabilities
Our DMPK team are proven experts in in vitro ADME testing who have completed thousands of studies for both small and large molecule development needs. Measuring the in vitro ADME properties of a drug candidate can provide an essential value for predicting its bioavailability and biological activity (i.e., whether a drug can reach its target and exhibit the corresponding therapeutic effect). With the support of our comprehensive in vitro ADME service platform, you can focus on optimizing your compound and efficiently and confidently move to the next stage.
Physical Chemical Properties
- Solubility, lipophilicity (LogD & LogP), pKa, buffer stability
Permeability
- PAMPA
- Caco-2, MDCK II, MDR1-MDCK II, BCRP-MDCK II, MDCK I, MDR1-MDCK I Monolayers
Transporter
- Efflux transporters: BCRP and P-gp transfected monolayers
- Efflux transporters BCRP, P-gp, BSEP, MRP1/2/3/4, as membrane vesicles
- SLC transporters: OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2, PEPT1/2, ASBT, NTCP MATE1, and MATE2-K
- Hepatocyte uptake experiments
Distribution
- Blood-to-plasma ratio
- Protein binding: Equilibrium dialysis, ultracentrifugation, and ultrafiltration
- Tissue binding
Metabolism
- Matrix stability: Tissue, plasma, SGF/SIF, etc
- Metabolic stability: Microsomes, S9, hepatocytes, cytosol, mitochondria and supersomes
CYP & Non-CYP Enzymes
- Cytochrome P450 (CYP) Reversible inhibition and time-dependent inhibition (single point, IC50, full characterizations including mechanism, Ki, kinact and KI)
- PXR/AhR Activation & CYP induction (activity and mRNA)
- CYP phenotyping
- UGT, FMO, SULT, etc. phenotyping
in vitro ADME Assay Automation
Assay automation establishes consistency and condenses process timelines during various steps, from sample preparation and reagent storage to compound identification. Additionally, margins of error can be significantly reduced through automated applications that take on repetitive tasks and data entry.
- Six liquid-handling systems (Tecan®, Hamilton®, Biomek®) for ADME assay automation
- Rigorous automated-assay validation
End-to-End in vitro ADME Solutions
Our in vitro services provide the data-driven support you need to design, select, and advance your compounds from discovery through IND-enabling milestones. Whether you need early development testing – for metabolic stability, kinetic and thermodynamic solubility, plasma protein binding and more – or a fully integrated program, our experts will collaborate with your team to understand your project needs and help 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 |
in vitro ADME FAQs
What is in vitro ADME testing?
In vitro ADME testing is to study absorption (A), distribution (D), metabolism (M), and excretion (E) properties of a drug candidate in a panel of assays utilizing test systems outside of a living organism. Here is what is assessed for each one:
- Absorption: A compound’s ability to pass through physiological barriers such as the intestines, skin, etc.
- Distribution: How a compound is distributed throughout the body or tissue once it has been taken into the body.
- Metabolism: How the body breaks down the compound in organs such as liver, kidney, skin, or the gut.
- Excretion: How the body removes the compound.
In addition, evaluations of drug-drug interaction potential are also part of the in vitro ADME studies. In vitro studies help drug developers understand if a drug candidate is suitable for further testing.
What assays are used for in vitro ADME testing?
- Absorption
PAMPA, Caco-2, MDCKII, MDR1-MDCKII, MDR1-MDCKI, MDCK I, BCRP, P-gp, BSEP, MRP2, MATE1, MATE2-K, OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2, PEPT1/2, and liver uptake experiments - Distribution
Red blood cell distribution: Blood/Plasma partitioning Ratio
Protein binding to plasma or tissue homogenates - Metabolism
Stability, metabolite generation, metabolite identifications, phenotyping in various matrices and species - Metabolism-related drug-drug interactions
CYP and UGT: Reversible inhibition, Ki, time-dependent inhibition, kinact/KI, metabolic reaction phenotyping, CYP enzyme induction (enzyme activity and gene-level) - Excretion
Transporters
How does in vitro ADME testing help drug developers?
In vitro ADME testing can provide early insight into the properties of a drug candidate, informing further testing strategy around areas such as chemical structure optimization, drug-like candidate selection, in vivo pharmacokinetics properties, and drug-drug interaction potential.
Need an in vitro ADME partner?
Whether you need a testing program tailored to your product or have questions about your ADME strategy, we can help.