Proteinbound

Proteinbound is a term used to describe molecules that are bound to proteins, most commonly in blood plasma or tissues. In physiology and pharmacology, many drugs, hormones, metal ions, and signaling molecules bind reversibly to carrier proteins such as albumin, alpha-1-acid glycoprotein, lipoproteins, or transferrin. The extent of binding is described by the protein-bound fraction, often represented as the unbound fraction (fu) or the bound portion (fb). The bound portion serves as a reservoir and generally remains inactive pharmacologically, while the unbound fraction is free to interact with targets, cross biological barriers, and be eliminated.

Binding can be saturable and influenced by drug concentration, competing ligands, pH, and the regulatory state of the binding proteins. Clinically, high protein binding tends to reduce the volume of distribution and slow clearance, prolonging a drug’s half-life, but also means small changes in free drug concentration can occur when displacement interactions happen. Drugs like warfarin, phenytoin, and many NSAIDs are highly protein-bound; displacement by another drug or a change in albumin levels can increase free drug exposure and risk of adverse effects.

In disease, low albumin or hypoalbuminemia decreases binding capacity, increasing the free fraction and potentially enhancing effects or toxicity. Pregnancy, aging, and critical illness can also alter protein binding. Pharmacokinetic analyses and dosing decisions often consider the protein-bound fraction to predict responses and interactions.

Measurement methods include equilibrium dialysis and ultrafiltration to estimate fu and fb. Understanding proteinbinding helps explain variability in drug response and the potential for interactions.