The evolution of accelerator mass spectrometry (AMS) applications in the life sciences over the past 10 years has driven new innovations in deploying very small doses of 14C-labeled drugs to answer key questions that often emerge during early clinical drug development.
Since AMS can measure levels of 14C-radiolabeled drug-related material that are 1,000 to 10,000 times lower than conventional LC-MS instrumentation, tracer doses of 14C-labeled drug can be administered that are below the level of concern from a radiation safety perspective.
This allows for very low doses of radioactivity to be a surrogate measurement for drug levels that cannot be detected by traditional measures after dosing, ultimately saving time and cost in drug development while enriching the information collected.
Celerion collaborates with the leading AMS service providers, to deliver solutions to the following drug development challenges:
- Assessment of absolute bioavailability for an oral drug: microtracer dose of intravenous radiolabeled drug given after administration of normal oral dose of cold drug. AMS follows intravenous PK. LCMS follows oral PK.
- Eliminates the need to create GMP intravenous formulation and associated animal safety testing to get measure of absolute bioavailability
- Assessment of ADME profile: microtracer dose added to cold dose provides answers to mass balance of drug elimination and metabolic profiles in excreta during the First-In-Human (FIH) studies
- Provides evidence for MIST regulatory guidance
- Assessment of distribution into human tissue fluids (e.g. CSF fluid for CNS, arthritic joint fluid, sputum/pulmonary lavage, saliva, tears, semen, milk, sweat)
- Detects presence of drug/metabolites in tiny sample volumes or at low concentrations at or near site of drug action or to define potential exposure for assessment of human drug safety
- Perform human ADME for long half-life drugs/metabolites by using microtracer amounts as the standard mass balance radioactivity dose given is too high for healthy subjects
- Avoids need for long-term confinements of study subjects
- Allows for a safe dose of radioactivity
- Obtain ADME information in patients who cannot be studied in a Phase I clinic
- Low level radioactivity allows for dosing in a hospital or outpatient setting
- Micro-dosing approach in getting early PK data under an Exploratory IND in the US (Phase 0 studies)
- Ideal for selecting go-forward clinical drug from several candidates
Celerion’s clinic in Lincoln, Nebraska, is the only Phase I facility in North America with proven experience to release radiolabeled drug to regulatory standards that has been formulated on site for intravenous use in humans. This is required to perform assessments of absolute bioavailability using the microtracer approach.