4.14 : Factors Affecting Protein-Drug Binding: Patient-Related Factors

Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.

Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and diazepam. In contrast, infants with increased drug binding and substantial renal clearance often need higher doses of drugs like digoxin for therapeutic efficacy.

Older people, marked by reduced albumin content and elevated levels of α₁-acid glycoprotein, undergo alterations in free drug concentration. These age-related changes impact drug binding and contribute to nuanced shifts in pharmacokinetics and pharmacodynamics.

Interindividual variations in drug binding are frequently attributed to genetic and environmental factors. Genetic predispositions play a pivotal role in dictating the individual's response to drug therapy, shaping the intricate landscape of protein-drug interactions.

Pathological conditions majorly affect protein content, thereby affecting protein-drug binding. Hypoalbuminemia (an abnormally low blood albumin level), stemming from aging, trauma, or burns, poses a substantial threat to binding efficacy. Similarly, hyperlipoproteinemia (an abnormally high blood lipid level) affects the binding of lipophilic drugs.

The factors governing protein-drug binding carry profound consequences for both pharmacokinetics and pharmacodynamics. Diminished plasma protein-drug binding culminates in increased concentrations of unbound drugs. This, in turn, amplifies drug clearance, triggers redistribution, and can accentuate therapeutic or toxic actions. The delicate balance in protein-drug binding becomes a critical determinant in the efficacy and safety of drug therapies.