Optimizing 14C-radiochemical doses for absorption, distribution, metabolism, and excretion studies: A predictive approach.

A simple method is described that uses pharmacokinetic parameters for an unlabeled drug to predict for a 14C-absorption, distribution, metabolism, and excretion study, the radiochemical dose consistent with the analytical instrument for quantitative profiling of circulating metabolites by scintillation counting. Analysis of mass balance studies for 19 drugs verified the predictive method and shows that many mass balance studies are conducted with radiochemical doses either substantially higher than required and inconsistent with the as low as reasonably achievable principle or inadequate to conduct profiling of plasma with the intended instrumentation. SIGNIFICANCE STATEMENT: The method to predict the radiochemical doses for 14C-absorption distribution, metabolism, and elimination (14C-ADME) studies enables research teams to select the radiochemical dose at which to conduct an ADME study consistent with the analytical instrument for plasma profiling and with the as low as reasonably achievable principle. Furthermore, it can also be used to assess whether a microdose or macrodose study is more appropriate.