ADME

 

Evotec and its subsidiary Cyprotex have an in-depth understanding of the numerous aspects of ADME to be assessed and addressed during the timely development of safe and effective drugs. 

From activities designed to optimise and ‘de-risk’ potential lead candidates, and guide selection of the most relevant pre-clinical tox species, to definitive radio-metabolism packages and Human Radiolabeled Studies (HRS) support, our ADME teams always strive to apply rational, tailored solutions using state-of-the-art technology and a thorough understanding of current regulatory requirements.

Our highly qualified team benefits from many years of hands-on experience (in silico, in vitro and in vivo) with a diverse range of molecules, both chemical and biological in origin, as well as many of the combinations/permutations in-between, against a considerable array of clinical indications.

Within Evotec’s site at Verona, GLP and international regulatory standards are applied to all ADME activities.   

The ADME capabilities can serve also as part of an INDiGO programme, Evotec’s solution designed to de-risk, select the optimal candidates and accelerate IND-enabling programmes. 

 

 

Our range of services and capabilities include:

  •  In vitro metabolic stability & metabolite profiling
  • In vitro plasma protein binding, blood cell partitioning and tissue binding
  • In vitro metabolic stability (microsomal stability, hepatocyte stability, S9 stability, plasma stability)
  • In vitro CYP and non-CYP phenotyping & inhibition
  • In vitro UGT phenotyping & inhibition
  • In vitro permeability (Caco-2, MDCK)
  • In vitro drug transporter interaction studies
  • In vivo PK (rodents and non-rodents)
  • PK regimen design, profile elaboration, interpretation
  • In vivo bio-distribution (rodents and non-rodents) including QWBA 
  • Dosing regimen design (infusion/loading dose calculations)
  • In vivo excretion balance (rodents and non-rodents)
  • Ex vivo metabolite profiling
  • Ex vivo metabolite profiling with cold material
  • MIST studies (clinical metabolic profiling –qualitative and quantitative evaluation- & tox-cover estimates)
  • Metabolite profiling of radiolabeled compounds in Human (HRS)

Our experience spans

  • Isotopic dilution/formulation of radio-dose
  • Diversified sample extraction processes
  • Chromatographic separation of metabolites (& semi-prep for NMR)
  • Metabolites quantification in biological matrices
  • Mass spectrometry / metabolite identification 
  • Enzymology (kinetics of activity & inhibition thereof)
  • Radiolabel placement consultation
  • Due diligence and risk register compilation
  • Toxicokinetic study design, elaboration and interpretation
  • DDI assessments and clinical strategy development

Mass spectrometry platforms

  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS) with either on-line or off-line radio-detection
  • Liquid chromatography-high resolution mass spectrometry (LC-MS, HRMS, IMS) with either on-line or off-line radio-detection)
  • Liquid chromatography (HPLC, UHPLC) with UV, DAD

Radio assay platforms

  • Radio-liquid chromatography high-resolution mass spectrometry (Radio-LC-MS, HRMS)
  • Liquid Scintillation Counting (LSC)
  • Microplate counting for radiometric detection
  • Quantitative Whole-Body Autoradiography (QWBA)

Areas of excellence

The ADME teams within Evotec and subsidiary Cyprotex provide a wealth of technical expertise and decades of experience in the field. 

One example is our highly specialised structural identification service. We have successfully helped lift the FDA ‘clinical-hold’ on projects with suspected metabolite-based toxicity through the design and implementation of integrated approaches for profiling, isolation and structural identification studies across species and test systems.

Our strong expertise within the drug-drug interactions field is also well recognised within the industry and we undertake many full regulatory DDI packages for our clients during the year.

Frequently tailored specific study designs with due consideration of the 3Rs are used to advance understanding of drug disposition and fully meet regulatory requirements and timelines, in order to empower clients with integrated data and a clear advancement strategy.

ADME activities can be standalone or part of fully-integrated packages, including all aspects of drug development in a single site (INDiGO).

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