Recent Advances in the Applications of Radioisotopes in Drug Metabolism,Toxicology and Pharmacokinetics

Abstract

Radioisotopes have proven to be an indispensable tool in biomedical research and have played a pivotal role in the investigation of absorption, distribution, metabolism and excretion (ADME) properties of new chemical entities over the past several decades. The main advantage of using radioisotopes in studying the disposition of new drug candidates is the ease of detection and the achievement of high sensitivity, especially when compounds with high specific activity are used. The recent advances and applications of radioisotopes in designing and conducting ADME studies and its impact in the field of drug metabolism and pharmacokinetics are discussed in this review.

Using a Tritiated Compound to Elucidate Its Preclinical Metabolic and Excretory Pathways in Vivo: Exploring Tritium Exchange Risk

“…Radioisotope use in biopharmaceutical research has been invaluable in definitively elucidating test compound excretory and metabolic pathways in animals (Dalvie, 2000). The most common radionuclide used for these studies is 14 C because of its synthetic versatility, safety relative to other radioisotopes, and favorable nuclear properties dictating optimal half-life and specific activity (McCarthy, 2000).…”

High Performance Liquid Chromatography‐Electrochemistry‐Electrospray Ionization Mass Spectrometry (HPLC/EC/ESI‐MS) for Detection and Characterization of Roscovitine Oxidation Products

“…The resulting metabolite is excreted directly by the kidneys or in the bile, or it can undergo a Phase II metabolism step, in which small and hydrophilic biomolecules, such as glutathione, are coupled to the Phase I metabolite [3]. A common approach is to use in vitro systems using hepatocytes or microsomes [4] or in vivo methods, in which various radioactively labeled drug compounds are administered [5]. There is an increasing interest in new methods that could provide reliable information on possible metabolites.…”

Neuroscience and accelerator mass spectrometry

“…1,2 Accelerator mass spectrometry (AMS) is an exquisitely sensitive mass spectrometric method for measuring rare isotopes, especially radioisotopes. The technique is primarily applied in geochronology to date samples using longlived radioisotopes that are detected independent of their decay products or half-life.…”