Pharmacokinetics with Radiolabelled Compounds
Pharmacokinetics (PK) with Radiolabelled Compounds Services
Pharmaron conducts clinical PK studies with 14C radiolabelled compounds to determine both extravascular (typically oral) and IV pharmacokinetic (PK) parameters. This includes absolute bioavailability (F), clearance (CL) and volume of distribution (Vd). Comparison of systemic total [14C] levels with parent drug concentrations in plasma over time provides additional information on the extent of metabolism (metabolic burden).
We also conduct human ADME (hADME) studies with 14C radiolabelled compounds to determine mass balance, rates and routes of excretion and metabolite safety to meet FDA MIST (Metabolites in Safety Testing) guidelines.
Pharmaron can help your team design studies and fully integrated programs that help to de-risk compounds in development. We can also assist with formulation and selection of lead candidates by providing vital pharmacokinetic and disposition data.
Capabilities
Standard Clinical Study Designs
- Intravenous pharmacokinetics (IVPK) and absolute bioavailability by infusing IV 14C microtracers simultaneously with a non-labelled therapeutic dose in Phase l study designs
- Validated LC-MS/MS and LC-AMS methods are employed to determine the PK of the non-labelled extravascular therapeutic dose (typically oral) and the PK of the labelled intravenous dose respectively
- PK and ADME of radiolabelled compounds in human Phase l AME studies using both LSC and AMS methodologies
- PK, excretion and bioavailability at sub-therapeutic levels in Phase 0 (microdose) oral/IV cross-over study designs
Emerging Clinical Study Designs
- In addition to plasma, analyze urine and/or feces for 14C parent and/or total radioactivity (TRA) for data on renal clearance and biliary excretion in 14C IV microtracer studies
- Investigate long-lived (long half-life) metabolites by validating methods that quantify both parent drug and key metabolites in the same assay to generate PK profiles for any metabolites of interest
- Quantify circulating metabolites and their abundance relative to parent drug by profiling plasma using LC-AMS methods
- Assess IVPK and absolute bioavailability at steady state by dosing subjects with multiple therapeutic doses of unlabelled drug prior to administration of the IV 14C microtracer dose
- Determine fraction of drug absorbed (Fa) in a two-period study design
Download PDF to learn more about Pharmaron’s Manufacture of 14C Radiolabelled Drug Substances and Drug Products for Clinical Studies.
