ADME, pharmacokinetics defined

The efficacious plasma or tissue concentration largely defines the course of ADM E optimization. Pharmacokinetic features have a significant impact on safety. Off-target effects often limit the use of efficacious doses, as they make safety margins too narrow. Thus, the combination of PK characteristics and off-target activities are largely responsible for an acceptable TI. 

Elimination is defined as the process of removal of the drag from the body, which may involve metabolism and/or excretion. These processes of absorption, distribution, metabolism and excretion (ADME) are called the pharmacokinetic processes (Figure 1.8). The pharmacokinetic aspects of a drug are obviously just as important as its pharmacodynamics, when considering therapeutic efficacy. 

ADME—absorption, distribution, metabolism, and elimination. These are the defining pharmacokinetic characteristics of how a drug is handled by the body. 

The traditional role of preclinical drug metabolism in pharmaceutical research has been to define absorption, distribution, metabolism, and excretion (ADME) of potential drug compounds for regulatory fiUngs. This role has expanded over the past 5 years to include support of early drug discovery. Consequently, the number of compounds whose ADME characteristics need to be defined has expanded the work now encompasses thousands of compounds annually rather than the traditional tens of compounds. At the same time, the focus has evolved from merely defining a compound s own fate in the body to include the identification of potential liabiUties, such as parameters that Unfit in vivo pharmacokinetics (PK). 

Pharmacokinetic processes are broadly defined as absorption, distribution, metabolism, and excretion, giving rise to the frequently used acronym — ADME. Each of these processes has a kinetic component and an extent component. The former refers to the rate of movement or how fast the process occurs over time, whereas the extent... 

Pharmacokinetic, toxicokinetic, and ADME studies. As a part of the toxicity studies, or in other studies, toxicokinetics should be performed. Toxicokinetics is defined as the generation of pharmacokinetic data in order to assess systemic exposure. These data can be used in the interpretation of toxicology findings and their relevance to clinical safety. For meaningful results to be generated, analytical methods must have been developed with the analytes (API, metabolites, etc.) and matrices (plasma, whole blood, tissue. 

---