In Vitro ADME / DMPK Screening

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By involving ADME / DMPK early in the drug discovery process you can ensure the best molecule is progressed. At Charnwood Discovery, not only do we have a range of in vitro ADME assays available, but we also have experts in different DMPK areas allowing us to offer a tailored approach to your project needs.

In Vitro ADME Assays that Ensure the Right Question is Answered

In vitro ADME assay

Our team collaborates with you to customize in vitro ADME assays that effectively address your specific project questions, as a standard practice. 

We also make ourselves available to consult with you. Whether you generate the data externally or in-house, our highly experienced team will review the data package, propose any necessary additional experiments, and assist in troubleshooting data issues. 
 
Our ADME / DMPK department continually expands the assortment of assays we offer. If you do not see the assay you need listed on our website, please inform us. We remain committed to meeting your project requirements, even for assays not currently listed. 

Physicochemical Properties

Developing new candidates that combine biological activity with appropriate physicochemical properties is one of the key challenges in the drug discovery process. Therefore, investigating the physical properties alongside the chemical properties of the drug substances is crucial in early drug discovery. 

Compound solubility is tested with our Kinetic Solubility assay developed using the MultiScreen® Solubility filter plates. No chromophore, no problem! This assay is available with either a UV or LC-MS end point.

Find more information on aqueous solubility here

To determine the partition co-efficient we use our Chromatographic LogD experiment, which offers a higher throughput than the traditional LogD shake flask assay.

Find more information on lipophilicity here

Permeability

Considering the drug’s permeability is a crucial aspect of the drug discovery process, particularly when aiming for oral delivery. The drug’s ability to cross the cell membrane depends on transporter proteins and membrane permeability.

At Charnwood Discovery, we can measure permeability using the following assays:

PAMPA is measured using Pion Inc’s kit technology, which consists of a membrane coated with lipid to mimic gastrointestinal conditions, allowing the evaluation of the passive permeability of a compound at a range of physiologically relevant pH values. 

Read more about PAMPA.

21-day differentiated cells are used as model for the human intestinal barrier as they differentiate and polarize to form tight junction and express transporter proteins (e.g., P-glycoprotein and BCRP). This allows for the assessment of both passive and active transport across the monolayer, and enables the determination of an efflux ratio of the test compound.

Find out more here

Metabolic Stability

Understanding the metabolism in drug discovery is essential. It influences how much compound is removed before it can exert a therapeutic effect, how long a drug will remain in the body, and the dosing strategy.

The primary organ responsible for the metabolism of drugs is the liver. The liver intrinsic clearance (CLint) is the measurement of the liver’s innate ability to transform and eliminate a drug from the body. This excludes factors such as hepatic blood-flow and protein binding.

Charnwood Discovery also offers metabolite identification. This can be from metabolic stability samples, enabling early identification of the most abundant metabolites. Alternatively, it can come from in vitro or in vivo samples later in the discovery process, allowing for a comprehensive determination of the metabolic profile.

In Vitro ADME / DMPK Screening

Liver Phase 1 metabolism is studied with the use of liver microsomes, a sub-cellular fraction, that are a useful tool for the in vitro assessment of intrinsic clearance. 

Other microsomal fractions can also be studied as required (intestinal or renal).

Find out more here.

Cryopreserved hepatocytes incubated in suspension contain both phase I (cytochrome P450s) and phase II metabolizing enzymes, as well as the necessary co-factors, enabling them to be used at Charnwood Discovery to study liver drug metabolism.

Find more information about our hepatocyte stability assay here.

Distribution

The Rapid Equilibrium Dialysis from Thermo Scientific™ (apparatus for performing equilibrium dialysis experiments in a high-throughput, automation-compatible format) is used at Charnwood Discovery to determine the protein binding of drugs.

Find out more here.

FAQs

Additional Services & Capabilities

In addition to in vitro ADME assays, Charnwood Discovery also offers the following services to support clients in identifying the best drug candidates and advancing their projects.

Our core capabilities, in addition to ADME / DMPK services, are

All Under One Roof!

Our compelling ‘under-one-roof’ service ensures that the best scientific minds can quickly and easily collaborate to move your project forward. We recruit from a global talent pool for diversity of intellectual input and, by investing in our scientists’ on-going development, they stay at the cutting edge of the latest advances.

ADME / DMPK