简体中文 English
In vitro ADME services can effectively provide evaluations of compounds’ absorption, distribution, metabolism, and drug interactions. These services aid in understanding the behavior of compounds within the human body, providing a critical basis for dosage setting, side effect predicting, and risk assessment during the development process.

In Vitro ADME Services

Our in vitro ADME services team offers a very wide services in the field of Physicochemical Properties, Permeability, Metabolic Stability, Drug-Drug Interaction, Transporter, and Protein Binding and Partitioning. We also have a variety of advanced automated liquid workstations and LC-MS/MS analysis technologies to further improve the assays' speed, quality, and throughput. More new modalities with complex structures have emerged from the recent R&D pipelines, including Proteolysis-Targeting Chimeras (PROTACs*), oligonucleotides, and antibody-conjugated drugs (ADCs). There are many challenges in the in vitro ADME study of these new modalities.

Overview

In Vivo Metabolite Identification
  • MetID in animal samples (plasma/blood, urine, feces, bile, tissue, etc.)
  • MetID in human samples (plasma, urine, feces, etc.)
    • MIST (metabolite in safety testing)
  • Metabolic soft spot analysis and identification
  • Reactive metabolite trapping (glutathione, cysteine, methoxamine, etc.)
  • MetID in liver microsomes
  • MetID in hepatocytes
  • MetID in S9
  • MetID in tissue homogenates
  • MetID in in vitro  plasma or blood

In Vitro Metabolite Identification
  • Solubility (KS, TS), pKa, logD, logP, and PSA

Physicochemical Property
Drug-drug Interaction
  • Metabolism-mediated drug interactions
  • Transporter-mediated drug interactions


  • PAMPA, Caco-2, MDCK I, MDR1-MDCK I, MDCK II, and MDR1-MDCK II
  • Ex vivo Franz cell-based dermal penetration assay

Permeability
Whole Blood/Plasma Distribution and Protein Binding
  • B/P ratio
  • Dialysis, ultracentrifugation, ultrafiltration, flux dialysis, competition dialysis, etc


Services

Typically, in the Lead Finding (LF) stage, compounds' solubility, lipophilicity, permeability, and microsomal stability are determined first. The obtained data are used to build the structure-property relationship of compounds, screen chemical structure categories, and confirm the priority of multiple structural backbones. At the Lead Optimization (LO) and Pre-Clinical Candidate (PCC) stages, comprehensive in vitro ADME studies are usually required. These include multi-species metabolic stability, plasma protein binding, transporters-related drug interaction, and inhibition of the drug-metabolizing enzymes combined with animal PK data to predict human PK performance. In the Investigational New Drug (IND) stage, a comprehensive evaluation of in vitro ADME properties is required and conducted per the requirements of drug registration authorities. It should be noted that the in vitro ADME screening study is usually not designed for regulatory submission purpose.

Metabolites in Safety Testing (MIST)
  • MetID in toxicology animal plasma from multiple ascending doses in a steady state
  • MetID in human MAD (multiple ascending doses) plasma in steady state
  • Compare the exposure of the major metabolites (with relative abundance ≥10% from human) between human and animal

Metabolite Biosynthesis and Structural Characterization
  • In vitro incubation biosynthesis of the target metabolites and their structural characterization
  • Animal in vivo biosynthesis of the target metabolites and their structural characterization



What does In Vitro ADME test study?

  • In vitro ADME studies absorption (A), distribution (D), metabolism (M), and excretion (E) properties of the drug candidates in a panel of assays outside of a living organism. The deions of each keyword are as follows. 
    • Absorption: Describes the compound’s ability to pass through physiological barriers such as the intestines, skin, etc.
  • Distribution: Describes how the compound is distributed throughout the body or tissue once it has been taken into the body.
  • Metabolism: Describes how the body breaks down the compound in organs such as liver, kidney, skin or the gut.
  • Excretion: Describes how the body removes the compound.

Our platform can also provide drug-drug interaction evaluation.

What is In Vitro ADME test?
In vitro comes from the Latin term "in glass". It refers to studies that are performed outside of a living organism in a controlled environment, such as a test tube or petri dish. In vitro studies are often contrasted with in vivo ("within the living") studies, which are done in a whole living organism.
The in vitro testing is ideal for testing a potential drug compound with well-controlled testing conditions at an early stage. In vitro testing requires less resources and tends to be much quicker than in vivo models. In vitro testing helps drug developers understand if the drug candidate is suitable to move forward with further investigations.


FAQs

How does metabolite profiling and identification assist in preclinical studies of drugs?    

The metabolite profiling and identification helps in understanding how the drugs are metabolized and eliminated from the body. It provides information on the metabolic pathways involved, the metabolites formed, and their relative abundance over time. This information is essential for optimizing drug dosing, predicting drug-drug interactions, and assessing the potential toxicity.

Understanding characteristics and structural assignments of the metabolites in different preclinical species (cross-species comparison) can help identify human-specific metabolites or those found at disproportionately high levels in humans in comparison to toxicity models. Comparing the in vitro and in vivo metabolism data of animals can determine if there is a good in vitro-in vivo correlation of metabolism, which can further ensure the reliability of using in vitro metabolism to predict in vivo metabolism in humans.

 What is the metabolite profiling and identification?                                               
The metabolite profiling and identification is the process of analyzing and characterizing the metabolites present in a biological sample, also known as the qualitative and semi-quantitative study of the biotransformation of a compound in in vitro and in vivo (animals and human). The parent drug is transformed into the metabolites by the action of biological enzymes (metabolic enzymes). Understanding the transformation can be helpful in anticipating of safety concerns arising from disproportionate toxic metabolites, predicting drug-drug interactions, and understanding routes of elimination.
 How soon can I expect to receive my metabolite identification results?
The timeline for receiving metabolite identification results depends on the complexity of the test compounds and the type of the assays. For regular small molecule compounds, the study can be completed in several days to two weeks during the early screening stage and generally takes four weeks for IND (Investigational New Drug) filing. For new modalities or special compounds, the process extends to approximately four to six weeks. It would be great to contact your study director if you have any questions about the availability of the study results.