14C Radiolabelled Studies - Human ADME (Macrotracer/Microtracer)

Human AME studies with radiolabelled compounds

14C Radiolabelled Studies – Human ADME (Macrotracer/Microtracer) Services

Pharmaron is a CRO specializing in integrating all elements of metabolism and PK programs for drugs in clinical development. This includes optimizing strategies for synthesis of radiolabels, sequencing of preclinical ADME/QWBA studies with the design and conduct of definitive 14C clinical studies for NDA submissions.

Additionally, we provide in-depth analytical support for parent drug and metabolite analysis including metabolite profiling, structure elucidation and identification of metabolites to determine metabolite safety and biotransformation pathways.

Integrated 14C Radiolabelled Clinical Studies in Healthy Volunteers

  • 14C hADME and 14C IV microtracers for absolute bioavailability (hABA) in either 2-period or 2-cohort clinical protocols to de-risk compound development
  • Clinical approaches that employ microtracer (low) or macrotracer (high) radioactive doses to achieve study-specific goals, optimize time, schedule of assessments, numbers of subjects/samples and radioactive exposure to labelled drug
  • Customized study design and consultation to address metabolites in safety testing (MIST guidance for FDA)
  • 14C-microtracer, macrotracer and hybrid protocols to optimize study design with compound-specific pharmacokinetics and distribution parameters that can conserve time and optimize sensitivity
  • Co-calibrated LSC and AMS analytical platforms to harmonize data outputs in hybrid designs
  • Integrated 14C/3H radiosynthesis, animal metabolism, hADME and metabolite identification
  • Radiolabelling strategy to ensure the radiolabel is located in a metabolically stable position in molecule

Radiochemical and Analytical Reports

  • NMR, MS and radio-chromatography to support radiosynthesis and confirm the highest quality 14C-API specifications
  • LSC and/or AMS for total radioactivity (total 14C) analysis to determine mass balance, rates and routes of excretion
  • Parent and 14C parent compound quantification by LC-MS/MS and LC-AMS (or LC-RAD or LC-TopCount®) respectively
  • Quantitative metabolite profiling by LC-RAD, LC-TopCount® and/or LC-AMS for fraction collection and analysis
  • Metabolite identification by HRMS to support both clinical and preclinical metabolism studies
  • Radio-pharmacy for 14C dose formulation and analysis (including stability and compatibility assessments)
  • Documented synthesis and formulation reports for 14C API (drug substance) and 14C dose formulation (drug product) including pharmacy manual for submission to FDA under open IND to satisfy CMC requirements to conduct 14C studies in human