Radiolabelled ADME consultant: ¹⁴C study design and interpretation

Radiolabelled ADME studies give the definitive picture of how a drug is absorbed, distributed, metabolised and excreted. They underpin metabolite safety (MIST) decisions, drug–drug interaction strategy and the ADME sections of your regulatory submissions. Done well, they answer these questions first time; done poorly, they can raise new ones late in development. I help sponsors plan, place and interpret radiolabelled studies from nonclinical through to human ADME.

Radiolabelled studies I support

• Label strategy: choosing a metabolically stable label position and working with radiochemistry providers on ¹⁴C or ³H synthesis.
• Nonclinical mass balance and excretion: recovery in urine, faeces and bile, including bile-duct cannulated studies.
• Tissue distribution: quantitative whole-body autoradiography (QWBA) and the dosimetry needed to set a safe human radioactive dose.
• Human ADME (hAME): mass balance, routes of elimination and circulating metabolite profiles in plasma and excreta.
• Microtracer approaches: accelerator mass spectrometry (AMS) designs, including intravenous microtracers for absolute bioavailability.
• Metabolite profiling and identification: radio-chromatography with mass spectrometry to identify major and disproportionate human metabolites.

How I can help

• Deciding when a radiolabelled study is needed and how it fits your development plan
• Designing protocols and selecting CROs and clinical units
• Reviewing data and reports, and resolving issues such as low recovery
• Linking ADME results to MIST, DDI and ICH M12 requirements
• Writing the ADME sections of IND Modules 2.6.4/2.6.5, Investigator’s Brochures and briefing books

Experience

I have more than 30 years in DMPK and ADME, including senior roles at Quotient Bioresearch (Chief Scientist), Covance and Envigo. My teams provided DMPK support to four successful NDAs, including Epidiolex, and I have particular expertise in cannabinoid DMPK.