How To Predict In Vivo Half-life And Clearance Of Your Test Compound With In Vitro Data?

by Iontox Biotechnology IONTOX
A metabolic stability assay is a critical in vitro screen often listed under the category of services known as ADME.

Many compounds that show promise with hitting their intended pharmaceutical target fail to move forward due to poor metabolic stability. A metabolic stability test offering to predict the half life clearance of a test compound is a critical assay, which, if used properly can prevent later stage compound failure due to the poor metabolic stability profile.

Why Screening Your Compound for Metabolic Stability is Important?

It is estimated that over 10% of drugs fail in clinical trials because of pharmacokinetic reasons, and the US Food and Drug Administration (FDA) guidelines emphasize the identification of metabolic pathways, relevant metabolites and potential drug-drug interactions for new chemical entities where metabolism is the main route of elimination.

Thus, drug metabolism studies are essential constituents of any drug development program.

Selecting a Contract Research Organization (CRO) to Run Your Metabolic Stability Study

In the metabolic stability assay, microsomes are exposed to various concentrations of the test compound for a number of exposure times, up to one hour (e.g. 5, 10, 20, 30, 45 and 60 minutes). These samples are centrifuged and the supernatant is analyzed via LC-MS/MS to determine the disappearance of the test compound over time (intrinsic clearance or CLint).

When screening for metabolic stability, in vitro, liver microsomes  are most commonly used. Liver microsomes are subcellular fractions that contain membrane bound drug metabolising enzymes.

However, while microsomes contain Phase I enzymes, primary human hepatocytes in sandwich culture contain both the Phase I and the Phase II enzymes. When seeking to run a metabolic stability assay for the most accurate data set consider a CRO that will  run the in vitro assay with primary human hepatocytes in sandwich culture.

The Metabolic Stability Assay from IONTOX

The metabolic stability assay from IONTOX utilizes microsomes and human primary hepatocytes in a sandwich culture.  In addition, when metabolic stability studies are combined with IONTOX’s Human Dynamic Multiple Organ Plate, clients can evaluate how one organ impacts the pharmacokinetics and pharmacodynamics of the test drug or chemical on multiple organs.

If you want to know the metabolic stability (half-life and clearance) of your test compound and run your organization’s metabolic stability assay effectively, then choose IONTOX’s in vitro Metabolic Stability assay.

For more information on Metabolic Stability, visit today.

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About Iontox Biotechnology Junior   IONTOX

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Created on May 1st 2020 14:07. Viewed 194 times.


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