Plasma Protein Binding (PPB) Assays
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Plasma Protein Binding Studies for Your Drug Candidate
Plasma protein binding is a quantification of the extent to which a drug attaches to proteins within the blood plasma. It is an important parameter to characterize the drug distribution process, as plasma protein binding may cause multiple effects, such as slowing down metabolism, reducing clearance, prolonging elimination half-life, and limiting drug distribution into target tissues. It is noteworthy that the concentration of the drug that remains unbound (free drug) at the therapeutic site is responsible for exerting the therapeutic effects.
As part of a full-scale preclinical program for drug discovery and development, plasma protein binding studies are of great significance in building the PK/PD models, predicting drug-drug interactions, evaluating drug toxicity, predicting human PK parameters and dosage regimens.
WuXi AppTec helps drug developers build ADME programs that include the right plasma protein binding assays and data-driven support needed to advance your compound from discovery to IND to NDA.
Accurate Plasma Protein Binding Testing
WuXi AppTec conducts more than 300,000 in vitro studies every year, with vast experience in plasma protein binding studies. With the support of WuXi AppTec’s comprehensive in vitro ADME service platform, you can get the quality data you need to optimize your compound and move into the next stages of development.
Plasma Protein Binding Assays
Plasma protein binding is often determined by various methods, including equilibrium dialysis, ultrafiltration, ultracentrifugation, flux dialysis, and more. The choice of method for plasma protein binding studies depends on various factors, including the specific drug properties, objectives of the study, and available resources. It is essential to carefully consider the strengths, limitations, and compatibility of each method with the drug under investigation to ensure reliable and valuable results.
This method utilizes a semipermeable membrane to effectively separate the free and bound drug fractions. The semipermeable membrane selectively permits the passage of unbound drug molecules, while effectively retaining the protein-bound drug within the plasma compartment.
Ultrafiltration is a technique used to distinguish and quantify the protein-bound and unbound drug fractions based on their varying molecular weights. This method involves passing the drug-containing sample through an ultrafiltration membrane with a specific molecular weight cutoff, allowing the smaller unbound drug molecules to pass through while retaining the larger protein-bound drug complexes.
Ultracentrifugation method uses an ultracentrifuge that operates at an extremely high speed, usually higher than 100,000 g, to separate free drugs from protein bound drugs in a tube that with no membrane. This method is useful for drugs that have problems with membrane effects, such as nonspecific binding and volume shifts.
The flux dialysis uses the same device as equilibrium dialysis to measure protein binding. It is based on the principle that the initial flux rate of a drug through a dialysis membrane is proportional to the product of the compound initial concentration, fraction unbound, and unbound dialysis membrane permeability. This method is useful for highly bound drugs that are difficult to reach equilibrium in equilibrium dialysis method.
Plasma Protein Binding Assays FAQs
Why does my drug development program need plasma protein binding assays?
Plasma protein binding plays an essential role in characterizing the drug distribution process, exerting various effects such as the modulation of metabolism, clearance reduction, prolongation of elimination half-life, and restriction of drug distribution into specific target tissues. Understanding and accurately assessing plasma protein binding are of great significance in the development of pharmacokinetic/pharmacodynamic (PK/PD) models, the prediction of drug-drug interactions, the evaluation of drug toxicity, and the estimation of dosage.
What are plasma protein binding assays?
Plasma protein binding assays measure the extent a compound binds to plasma proteins. The concentration of the drug that remains unbound at the therapeutic site is responsible for exerting the therapeutic effects. Drugs bind to plasma proteins to varying degrees, which impacts the ADME (absorption, distribution, metabolism, and excretion) properties of the drug in the body and the pharmacodynamic behavior of the drug.
What is the turnaround time for plasma protein binding assays at WuXi AppTec?
The turnaround time for plasma protein binding assays in drug development can vary depending on several factors, including the complexity of the drug molecule and the specific assay method used. Typically, the turnaround time for plasma protein binding assays can range from a few days to several weeks.
At what stage of drug development do I need plasma protein binding assays in my testing program?
Plasma protein binding assays are conducted in discovery ADME, IND-enabling ADME, and NDA-enabling ADME stages. They are important studies used to calculate various pharmacokinetic (PK) properties that inform future in vitro and in vivo ADME study designs.
What techniques are used to measure results from PPB assays?
Plasma protein binding can be measured using techniques like equilibrium dialysis, ultrafiltration, ultracentrifugation, and flux dialysis. The selection of method depends on various factors, including the specific drug properties, objectives of the study, and available resources. It is essential to carefully consider the strengths, limitations, and compatibility of each method with the drug under investigation to ensure reliable and meaningful results. Among these techniques, equilibrium dialysis is the most widely used approach for determining plasma protein binding.