Factors Affecting Protein-Drug Binding: Drug-Related Factors

Protein-drug binding can be affected by various drug-related factors.

The degree of protein binding is closely related to a drug's lipophilicity, with more lipophilic drugs exhibiting higher binding. For instance,  highly lipophilic cloxacillin binds to proteins at a 95% efficiency, while less lipophilic ampicillin binds at only a 20% efficiency.

Highly lipophilic drugs tend to localize in adipose tissues.

Additionally, drug ionization influences protein binding. Anionic drugs like penicillin G preferentially bind to human serum albumin or HSA, while cationic drugs like imipramine bind to α₁-acid glycoprotein or AAG. Unionized drugs exhibit stronger binding to lipoproteins.

The extent of protein-drug binding fluctuates with drug and protein concentrations.

While drug concentration has a limited effect on HSA binding as therapeutic concentrations are generally insufficient to saturate it, AAG can be saturated by lidocaine at therapeutic levels due to its lower blood concentration.