Human AME (hAME) Studies with Radiolabelled Compounds

human AME (hAME) with radiolabelled compounds

Human AME (hAME) Studies with Radiolabelled Compounds

Pharmaron is a Clinical Research Organisation (CRO) offering comprehensive human AME services to support a wide range of 14C radiolabelled studies in humans including mass balance, metabolite profiling/metabolite identification (MetID), absolute bioavailability (ABA) and IVPK. We are unique in providing fully integrated solutions that include radiosynthesis, in vitro and preclinical ADME, QWBA, human dosimetry, 14C dose formulation,  radio-analysis including AMS and the conduct of your definitive 14C human clinical studies.

Ultra-sensitive AMS and HP(UP)LC+AMS analysis can be utilized for the quantitation of total radioactivity and 14C parent/metabolites in human metabolism and absolute bioavailability clinical studies. Phase l clinical protocols can include either microtracer or macrotracer doses of radioactivity and employ both LSC and AMS analytical support. Hybrid study designs can take advantage of LSC analysis for early time points and AMS analysis for later time points.

We also offer Phase 0 microdose studies under an eIND (exploratory investigational new drug) to evaluate the PK and excretion of early-stage compounds. 14C studies can be conducted at Phamraron’s Clinical Pharmacology Center (CPC) in Baltimore or we can support third-party clinical research units (CRU).

Human AME studies (hAME) | 14c radiolabelled studies

Clinical Protocols

  • Absorption, Metabolism, Excretion (hAME) –  Low 14C radioactive dose microtracer studies administering ~1-5 µCi of radioactivity compounded with a therapeutic, pharmacologically-relevant mass dose
  • Absorption, Metabolism, Excretion (hAME) – High 14C radioactive dose macrotracer studies administering ~100-200 µCi of radioactivity compounded with a therapeutic, pharmacologically-relevant mass dose
  • Absolute Bioavailability (hABA) – Low 14C radioactive IV microdose studies administering ~1-5 µCi of radioactivity intravenously concomitant with a therapeutic extravascular mass dose administered by the intended therapeutic route
Human AME studies with radiolabelled compounds

Radiolabelled Metabolism Studies

  • Phase l hAME studies employing 14C macrotracers or 14C mictrotracers
  • Mass balance, metabolite profiling and metabolite identification for metabolite safety testing (MIST)
  • IV 14C microtracers for hABA
  • Phase 0 microdosing studies under eIND
  • Ultra-sensitive 14C total radioactivity by AMS, metabolite profiling and 14C-parent/metabolite quantitation by LC-AMS
  • Metabolite identification (MetID) by HRMS

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GMP Radiosynthesis | human AME hAME

Radiosynthesis

  • Standard 14C and 3H radiosynthesis
  • GMP preparation of both 14C-drug substance and 14C-drug product
  • Non-GMP clinical-grade re-purification of 14C-drug substance for dose formulation in human microtracer studies
  • 14C and 3H radiolabelling of large molecules e.g. oligonucleotides, peptides, proteins
  • Expert metabolism and biotransformation advice for position of label in molecule

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Download PDF to learn more about Pharmaron’s Integrated Radiolabelled Metabolism & PK Programs.

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