• Bioavailability is one of the essential tools in pharmacokinetics.
• Regulatory authorities have provided guidance for bioavailability information for orally administered drug products in new drug applications.
Typical bioavailability studies (non-AMS) are costly and challenging. Without AMS, bioavailability studies are generally conducted using a two-way crossover design, thus requiring dosing times sufficiently separated to ensure clearance between the two dosing modes. Additionally, preparation of an IV formulation for a cross over study design presents a significant obstacle.
These issues can be overcome using a microdose design which incorporates 14C labeled drug product at sub-pharmacologic concentrations (<100 µg), with a pharmacologic oral dose of cold drug product simultaneously. Microdosing allows for parallel oral and IV assays performed on single PK specimens as well as easing the IV formulation challenges. Accelerator mass spectrometry allows for the routine, precise, and accurate quantitation of the sub-pharmacologic concentrations of a drug product.
AMS methods can be used to generate the IV area under the curve (AUC), whle standard LCMS/MS metheods can still be used to generate the oral AUC. Bioavailability is calculated by normalizing the IV AUC to the oral dose size and calculating the ratio obtained from the oral AUC and the normalized IV AUC.
14C label studies allow for an elegant assessment of absolute bioavailability in human subjects, eliminate variability introduced in crossover designs, and reduce the number of specimens that must be collected and time study subjects spend at the clinic. 14C label studies also avoid the challenges of developing IV formulations at pharmacologic concentrations. All of this translates into shorter release timelines and fewer incurred costs.
Accium BioSciences has has successfully delivered on a wide range of AMS based absolute bioavailability balance studies. Each study is customized to address particular challenges specific to each program.