{"id":5716,"date":"2022-08-01T08:04:28","date_gmt":"2022-08-01T13:04:28","guid":{"rendered":"https:\/\/labtesting.\/?p=5716"},"modified":"2023-07-10T10:27:23","modified_gmt":"2023-07-10T15:27:23","slug":"in-vivo-adme-testing-in-drug-development-a-short-guide","status":"publish","type":"post","link":"https:\/\/labtesting.\/2022\/08\/01\/in-vivo-adme-testing-in-drug-development-a-short-guide\/","title":{"rendered":"In Vivo ADME Testing in Drug Development: A Short Guide"},"content":{"rendered":"\n
In vitro and in vivo ADME studies provide valuable data about a test article as it moves through preclinical development<\/a>. In this short guide, we provide an overview of in vivo ADME testing, including why it\u2019s important and how it works.<\/p>\n\n\n\n For a successful Investigational New Drug (IND) submission, drug developers need to put together a complete data package that includes in vivo studies. An IND package requires an assessment of<\/a> the pharmacokinetics and biological disposition of the test article in animals and information on the ADME properties of the test article, if known. This typically starts with in vitro testing<\/a> before moving on to in vivo ADME testing.<\/p>\n\n\n\n The data generated from in vivo ADME studies provide a more complete picture of safety and risk \u2013 and make the test article more compelling for clinical approval. As a result, in vivo ADME studies are required to file a New Drug Application (NDA).<\/p>\n\n\n\n In vivo ADME studies are generally conducted with radioactive labels on the target test article to provide quantitative information on the mass of distribution, rate of metabolism, and pathway of excretion for the test article and its metabolites.<\/p>\n\n\n\n While in vitro ADME studies<\/a> are performed outside of a living organism in a controlled environment, in vivo studies are done within a living system. Researchers also conduct ex vivo studies, in which samples of tissues, cells, blood or plasma are collected from an in vivo system but experimented on or investigated outside of the natural in vivo environment. The information gleaned from in vitro ADME assays help researchers and developers move forward with ex vivo and in vivo studies.<\/p>\n\n\n\n In vivo ADME falls under the Drug Metabolism and Pharmacokinetics (DMPK<\/a>) umbrella following an understanding of the test article\u2019s toxicology. While some in vivo ADME testing can occur early on in discovery, most in vivo tests typically happen later in the stage of optimizing the structure and properties of the test article. They are sometimes one of the last studies conducted prior to first-time radiolabeled clinical studies.<\/p>\n\n\n\n Later-stage in vivo ADME studies administer radiolabel test articles to living systems. Radiolabeled test articles incorporate a radioisotope that allow researchers to track the passage of a molecule through the system. After dosing, you can examine ADME properties:<\/p>\n\n\n\n Understanding these properties in vivo is critical as you prepare to take a test article to clinical studies. Here\u2019s what the testing process usually entails. <\/p>\n\n\n\n In vivo ADME studies start by looking at the pharmacokinetics (PK) of the test article, the characterization of the time course of the test article being absorbed, distributed, metabolized and excreted.<\/p>\n\n\n\n To characterize the movement of the test article into the body (absorption), researchers analyze the test article concentration in plasma, blood and tissues.<\/p>\n\n\n\n QWBA determines a test article’s tissue distribution, both visually and quantitatively. A living system is dosed with a radiolabeled test article and then radioactivity measured through cross section slides to show distribution in tissues over time.<\/p>\n\n\n\n Mass balance and BDC studies<\/a> characterize how the test article is eliminated from the test system \u2013 specifically the test article\u2019s excretion path and rate. The test system or in vivo system and samples are analyzed for radioactivity, providing insight into how the test article is eliminated from the body.<\/p>\n\n\n\n To understand the metabolic pathways in the animal system, researchers collect urine, feces and bile samples from mass balance studies and send them for metabolic profiling and identification<\/a>. These studies are used to discover what metabolites are formed following test article distribution to ensure that there are not any potentially harmful human-specific metabolites.<\/p>\n\n\n\n The previously listed in vivo ADME tests provide the data needed in preparation for human radiolabel absorption, metabolism, excretion (AME) studies<\/a>. Human AME studies help drug developers understand the nature and amounts of drug metabolites formed in the human body, and the data reveals the biotransformation, disposition, and clearance of the parent test article and its metabolites. These studies are crucial to guide the design of clinical drug-drug interactions and the dose level selection in phase II and II clinical trials.<\/p>\n\n\n\nWhat Is in vivo<\/em> ADME Testing?<\/h3>\n\n\n\n
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What Results Do in vivo<\/em> ADME Testing Studies Provide?<\/h3>\n\n\n\n
Absorption: Pharmacokinetics<\/h4>\n\n\n\n
Distribution: Quantitative Whole Body Autoradiography (QWBA)<\/h4>\n\n\n\n
Excretion: Mass Balance & Bile Duct Cannulated (BDC)<\/h4>\n\n\n\n
Metabolism: Metabolic Profiling<\/h4>\n\n\n\n
Human AME Studies<\/h4>\n\n\n\n
Common in vivo<\/em> ADME Testing Challenges<\/h4>\n\n\n\n