Plasma protein binding (PPB) evaluations

Record Type: Evaluation

Once a drug is absorbed into the circulation, it can bind to plasma proteins. The two major plasma proteins in humans are serum albumin, which predominantly binds neutral and basic drugs, and α1-acid glycoprotein, which predominantly binds acidic drugs (such as acetyl salicylic acid - aspirin).

Plasma protein binding (PPB) influences pharmacokinetic (PK) parameters, particularly volume of distribution and clearance. High PPB limits the partitioning of drugs from the blood into the tissues where they exert a therapeutic effect.

Drug PPB forms a "reservoir" of the drug and extends the half-life because only the free drug can be metabolized. 

Methods to assess PPB include equilibrium dialysis (most commonly used), ultrafiltration, ultracentrifugation, gel filtration, binding to albumin microspheres and circular dichroism. In equilibrium dialysis, a semi-permeable membrane separates a protein-containing compartment from a protein-free compartment and the test compound present in each compartment is quantified by liquid chromatography with tandem mass spectrometry (LC-MS-MS).



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