The duration of a therapeutic agent in the circulation of a subject depends on a variety of factors. Typically, the persistence of any agent in the circulatory system is characterized as a quantifiable pharmacokinetic value, such as the half-life (t1/2). Depending on the particular agent, some of the more obvious factors that may affect its half-life include, but are not limited to, the sensitivity of the agent to various plasma or liver degradative activities (e.g., proteolytic, glycolytic), the solubility of the agent in the blood, the immunogenicity of the agent, the ability of the liver to filter out the agent, and the ability of it to bind to one or more serum binding proteins (e.g., serum albumin).
For many candidate therapeutic agents, the pharmacokinetic half-life is of critical importance in determining whether such candidate molecules can be developed into efficacious therapeutic agents. Thus, no matter how active a candidate molecule may appear to be toward a desired target in a high-throughput screening program such a molecule may actually have little therapeutic value if it lacks an in vivo half-life that allows the molecule to persist sufficiently long in the circulation of a subject to achieve a proper steady state concentration in order to provide a desired therapeutic benefit. Accordingly, at some point in the screening process for candidate therapeutic agents, an indication of the pharmacokinetic in vivo half-life of each prospective candidate molecule must be assessed in order to eliminate from the process those molecules that have undesirable in vivo half-lives.
Typically, the first indication of whether candidate molecules may have an acceptable in vivo half-life is obtained using small mammals, such as rats or mice. However valuable such small mammal in vivo half-life studies may be, such procedures add considerable human labor, time, and expense to the screening process. Clearly, the screening process for new therapeutic agents could be made more efficient and more economical if there were available a reliable and simple in vitro means to determine whether candidate molecules have pharmacokinetic in vivo half-lives that warrant their continued inclusion in a drug development process.
USPTO Backgrounds
USPTO Backgrounds