Is Ticlopidine a Suitable Control Compound for Assessing PPB?

Plasma protein binding (PPB) is a vital parameter to determine during the drug discovery process, influencing both the pharmacokinetics and pharmacodynamics of a molecule. The major proteins of blood plasma that interact with drugs are human serum albumin (HSA) and α-acid glycoprotein (AAG), at concentrations of 600 µM and 12-30 µM respectively.

The two major binding sites of HSA show a preference for acidic drugs, and AAG for basic and neutral drugs, with its concentration also influenced by states of disease. Whilst plasma protein binding data alone is not sufficient to base optimisation on, it is required to interpret in vivo data in order to predict drug distribution; only the free drug is available for interaction with the target, and only the free drug is available to be cleared.

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