In Vitro ADME

Expert study designs, in vitro ADME assays and data interpretation from the in vitro ADME services group at Charles River allow you to characterize your drug candidate's ADME properties and its potential for drug interactions. 

Discovery

Charles River has focused on building efficient systems and procedures to meet the needs and timelines of clients working in the drug discovery environment. Many of our in vitro assays have multiple formats available to suit the different stages of the drug discovery pipeline, allowing us to offer a flexible approach to our ADME services. We offer a range of study design levels (SDLs) in our in vitro assay services. Each of our in vitro assays can be offered as an early screening (single time point or concentration) or a more definitive (IC50 or T1/2) study to estimate PK/ADME characteristics.

Development

In vitro ADME assays are an important part of a successful drug development program aiding in the critical decision making process by offering metabolic information about drug-drug interactions, pharmacokinetics, absorption and potential toxicities. Our wide range of automated in vitro assays can be performed under GLP conditions, if required, yielding information in the areas of metabolism, toxicity and physicochemical characteristics.

While Charles River has standard procedures for each of these assays listed below, our team of experienced study directors can also assist in designing the best strategy and protocols customized to suit any drug discovery need.

CYP450 Inhibition
  • Human liver microsomes or recombinant enzymes
  • Major CYP450 isozymes: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 and 2E1
  • Reversible, metabolic and time-dependent inhibition (IC50 shift)
  • Initial screening assessments (% inhibition) or definitive determinations (IC50, Ki)
  • Kinact/KI determinations
  • Determine formation of MIC and/or covalent binding
  • Activity of CYP450 isoforms measured via LC-MS/MS analysis
  • Drug-drug interaction experiments
CYP450 Reaction Phenotyping
CYP450 Induction
Protein Binding — Rapid Equilibrium Dialysis (RED), Ultrafiltration or Ultracentrifugation (UC)
Melanin Binding
Metabolic Stability — Microsomes, S9
Metabolic Stability — Hepatocytes
Metabolite ID/Profiling
Matrix Stability (Matrix, Buffer)
Red Blood Cell (RBC) Partitioning (Blood/Plasma Ratio)
Permeability and Efflux (Caco-2, MDCK, MDCK-MDRI, MDCK-BCRP)
Influx Transporters
Herg Inhibition
Cell Proliferation and Cytoxicity

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Lead Optimization & Candidate Selection

We are able to consistently deliver high-quality development candidates (over 70 since 2001) within industry standard timelines, including the data required to support progression into IND studies.