- Metabolic Stability
- CYP Interaction
- Permeability & Transporters
- Physicochemical Properties
- Protein Binding
Discovery PK and Toxicology
Frontage offers multiple customizable protein binding assays to determine the true amount of available drug responsible for pharmacological activity. The binding of a drug to plasma (and tissue) proteins is critical to understanding the properties of the drug. This affects pharmacodynamics since only the free (unbound) drug is responsible for pharmacological activity.
When drugs are lipophilic and can permeate red blood cells, it becomes crucial to assess the blood distribution of compounds. This helps determine the most appropriate matrix for analysis of the compound concentrations in circulation. If there is an accumulation of the compound in red blood cells, this may reduce the amount of available compound needed to cause the desired pharmacological effect.
In most cases, plasma protein binding (PPB) is measured using undiluted human or animal plasma. In some cases, a semi-mechanistic investigation of the roles of certain plasma proteins may offer some insights into understanding compound PK profiles.
Most Common Drug-Binding Proteins:
Acidic and neutral compounds generally tend to interact with albumin, while basic substances may prefer binding to the acidic AAG molecule. Frontage has done detailed binding characterizations of compounds to AAG and human serum albumin (HSA).
In addition to binding to plasma proteins, drug candidates can also bind to various tissues, such as the brain and liver. The extent of tissue binding may affect the distribution of the drug to the tissue and its duration, both of which are important for safety and pharmacodynamic effects. Frontage labs can process liver, kidney, and many more types of tissues.