Predict In Vivo Half-life and Clearance of Your Test Compound with Metabolic Stability Assay

In the early phases of drug discovery determination of metabolic stability of new chemical entities is an important step, since it influences pharmacokinetic properties of therapeutic compounds.

In the process of drug discovery, new chemical entities can’t be directed to humans; hence, the predictions of these properties must be made from In Vivo method. Therapeutic compounds can be divided into those which metabolizes faster and those which undergo relatively slow biotransformation.

Fast biotransformation rate minimizes exposure to the maternal compound and may lead to the generation of active, nonactive or toxic metabolites. On the other hand, high metabolic stability may promote interactions between drugs and lead to parent compound toxicity.

In vitro methods represent a significant alternative to animal testing, particularly when a huge number of new chemical entities( NCEs) need to be evaluated and when a small number of testing compounds are available. Preliminary in vitro data give the opportunity of targeted synthesis of compounds with favorable metabolic profiles, thus leading to noteworthy time and cost reduction.

Why Metabolic Stability of Your Test Compound is Important?

Metabolic stability measurement is a crucial component of preclinical drug development process. It is noted that over 10% of drugs fail in clinical trials because of pharmacokinetic reasons. The aim of metabolic stability study is measuring the disappearance rate of a test compound. The half-life, in vitro clearance measured from metabolic stability assay can be utilized to determine hepatic clearance, and also to predict dose, toxicity level, oral bioavailability, etc.

The liver is the main organ for drug metabolism in the body. The liver subcellular fraction, microsome is a vital model for drug metabolism studies. It contains numerous drug metabolizing enzymes - P450s, FMOs, and UGTs. Metabolic transformation of a drug taking place in the liver can change significantly its efficacy, which may be harmful to the human body. Due to this, drug candidates are tested early in the drug discovery for metabolic stability.

How IONTOX's Metabolic Stability Assay Predicts the In Vivo Half-life and Clearance of Your Test Compound?

An important early ADME test, Metabolic Stability Assay from IONTOX uses microsomes and human primary hepatocytes in a sandwich culture.

Microsomes contain Phase I enzymes and the primary human hepatocytes in sandwich culture contain both the Phase I and the Phase II enzymes. The microsomes and/or primary human hepatocytes in sandwich culture are exposed to the test compound for a number of exposure times, up to one hour and the samples are then evaluated by LC-MS/MS to determine intrinsic clearance of your test compound.

When combined with the Human Dynamic Multiple Organ Plate, IONTOX's Metabolic Stability assay assesses how one organ impacts the pharmacokinetics and pharmacodynamics of the test drug or chemical.

So, if you want to know the metabolic stability (half-life and clearance) of your test compound, then choose highly effective IONTOX’s In Vitro Metabolic Stability assay.

To know more about Metabolic Stability, visit iontox.com today.

Report this Page