Abstract

Human ADME (Absorption, Distribution, Metabolism, and Excretion) studies of new chemical entities are an important part of the drug development process. These studies are normally performed by using a radioactive tracer (C-14 or H-3) blended with a therapeutic dose of non-radioactive drug in about four to six subjects. The radiolabeled API (Active Pharmaceutical Ingredient) is utilized to evaluate the recovery and track the metabolic fate and physiological disposition of the drug. More challenges are faced regarding subject and site selection and supply of C-14 labeled drug product when performing these studies with oncology compounds. If the compound is suitable to study in healthy volunteers, the strategy employed will be similar to what is normally conducted with non-oncology compounds. But if the compound is not suitable to study in healthy volunteers (e.g. a cytotoxic drug), different strategies including recruitment of patients and availability of pure radioactive drug product whenever a patient becomes available for the study must be employed. These studies generally extend over a period of six months to a year. Because of this, stability studies of manufactured radiolabled compound assume importance. Two approaches ((Microtracer-AMS (Accelerator Mass Spectrometry) and the traditional method) used for these studies will be described. Detailed information will be explained by using three examples (Compounds A, B, and C, with microtracer - AMS method in healthy volunteers, microtracer - AMS method in patients, and traditional method in patients respectively).

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