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Blood Plasma Partitioning

Certain drugs are highly bound to red blood cells (RBC) whilst others are highly bound to plasma proteins. As pharmacokinetics are mostly measured from plasma samples, binding to RBC can lead to dramatically miscalculated blood-derived pharmacokinetic parameters, e.g. clearance, AUC, Cmax and Vss.

Like plasma protein binding, binding to red blood cells (RBC) can significantly reduce a drug’s free plasma concentration, i.e. the fraction of drug that is available for its pharmacological action and its elimination. A compound’s pharmacodynamic and pharmacokinetic profile can hence be severely affected by its blood partitioning. Likewise, accumulation in RBC can lead to toxicity in these cells. It is, therefore, important to determine blood partitioning early during the drug discovery process.

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