When evaluating the pharmacokinetics (PK) and ADME of candidate drug molecules, the degree of binding of therapeutic compounds to plasma, serum proteins or microsomes has a significant effect on the concentration of free unbound drug in vivo, which in turn affects the amount of drugs distributed to tissues in the body. This can have a significant impact on drug efficacy and metabolism. BOC Sciences offers integrated drug distribution assays that allow you to better understand the plasma protein binding properties of effective drug molecules. With our extensive experience in the DMPK/ADME field and state-of-the-art scientific equipment, we focus on providing flexible solutions with cost-effective, high-quality, reproducible data and fast turnaround times.
Generally, drug distribution refers to the transfer of drug molecules through the blood to various tissues in the body. Different body parts have different doses of drug molecules and different retention times. Theoretically, the physicochemical properties of drugs, such as water solubility, lipophilicity, and stability, can determine whether a drug tends to stay in liquid or lipid tissues. Drug permeability is another factor affecting in vivo distribution, as drugs with different penetrating abilities result in differential distribution volumes. In addition, the binding of drug to tissue or plasma proteins is a third factor affecting drug distribution. When drugs are tightly bound to proteins in the blood, it is difficult to leave the bloodstream into the tissue. However, some drugs can also prolong their effects when they accumulate in certain tissues for a long time.
Binding of test compounds to plasma proteins is an important factor affecting drug efficacy, metabolism, and pharmacokinetic properties. In many cases, drug efficacy depends on the concentration of free (unbound) drug rather than the total concentration in plasma. If the drug is highly bound to plasma proteins, the amount of drug available to reach the target is reduced. Subsequently, the efficacy of the compound may be significantly reduced. Therefore, information on free drug moieties is critical for drug development and may help correlate with in vivo efficacy. BOC Sciences' plasma protein binding employs strategies such as rapid equilibrium dialysis, ultrafiltration and ultracentrifugation to assess the percent binding of compounds to plasma proteins of human and preclinical species.
Since drug molecules selectively bind to plasma proteins in the blood, plasma concentrations may differ from whole blood concentrations. Therefore, testing the distribution ratio of blood to plasma can help to understand whether compounds enter and bind to proteins in blood cells. The plasma partition assay from BOC Sciences provides a specific and robust assay to measure these parameters using fresh blood from human and preclinical species.
Depending on their physicochemical properties (such as lipophilicity and solubility), drug molecules can bind to different kinds of tissues, such as the brain, lipids, liver, and kidney, resulting in the accumulation of compounds in vivo outside the blood circulation. Accumulation in tissues will affect the pharmacokinetics of the compound and may prolong the body's exposure to the compound, leading to toxicity. BOC Sciences' brain tissue binding assay uses rapid equilibrium dialysis (RED) to measure the percent binding of test compounds to brain tissue, and samples are analyzed by LC/MS/MS.
Subcellular fractions such as liver microsomes can be used to study hepatic clearance and in vitro models of drug-drug interactions. Multiple studies have demonstrated that knowledge of the extent of microsomal binding contributes to a better understanding of the relationship between in vitro metabolism and in vivo pharmacokinetics. With extensive DMPK/ADME assay capabilities, BOC Sciences provides kinetic measurements using liver microsomes to predict in vivo metabolic clearance of compounds in humans.
When combined with our comprehensive portfolio of bioavailability assays, BOC Sciences' drug distribution assays can be used to help you prioritize compounds for further development. Our protein binding assays are available for testing in standard human and animal plasma. If you are interested in our drug distribution testing services, please contact us for more information.