Plasma Protein Binding of Drugs in the Elderly

Abstract

Binding to plasma proteins can affect the pharmacokinetics and pharmacodynamics of drugs. Age is one of many factors which can affect plasma protein binding of drugs. Unfortunately, very few generalities can be drawn from the studies of the effect of age on protein binding. Whether age has an effect on protein binding is dependent not only on the drug, but also on the manner in which the study is conducted. Several studies involve patients with various disease states making assessment of the effect of age alone on protein binding difficult. Results of different studies on the same drug do not always agree--in one case finding no change in protein binding with age and in another, a significant increase or decrease in protein binding. Most drugs which exhibit increased binding (decreased free fraction) in elderly subjects are basic and tend to have a greater affinity for alpha 1-acid glycoprotein than for albumin. The list of drugs exhibiting decreased binding (increased free fraction) in the elderly is longer and includes both acidic and basic drugs. The impact of changes in protein binding with age is dependent on the magnitude of the change, on the pharmacokinetic characteristics of the drug and on its therapeutic index. Some changes, although statistically significant, are not likely to be of importance clinically. From the studies reviewed, the free fraction is changed by greater than 50% in the elderly for only a few drugs, e.g. acetazolamide, diflunisal, etomidate, naproxen, salicylate, valproate and zimeldine.

Aging Biology and Geriatric Clinical Pharmacology

“…Overall, age-related effects on protein binding have minimal clinical significance (Schmucker, 1979;Wallace and Verbeeck, 1987;Bernus et al, 1997;Grandison and Boudinot, 2000;Benet and Hoener, 2002). There is a reduction in blood albumin concentration of about 10% in older people (Greenblatt, 1979;Campion et al, 1988) and possibly an increase in ␣1-acid glycoprotein (Verbeeck et al, 1984), probably secondary to age-associated inflammatory disease (Grandison and Boudinot, 2000).…”

Epilepsy in the Elderly

“…Drug concentration at the site of action determines the magnitude of both desired and toxic responses. The unbound drug concentration in serum is in direct equilibrium with the concentration at the site of action and provides the best correlation with drug response (12). Total serum drug concentration is useful for monitoring therapy when the drug is not highly protein bound (less than 75%) or when the ratio of unbound to total drug concentration remains relatively stable.…”

Stereoselective binding of propranolol in the elderly.

“…The main source of propranolol binding in serum has been shown to be with ot -acid glycoprotein (Vestal et al, 1979b;Rigby et al, 1985;Bendayan et al, 1984;Wallace & Verbeeck, 1987;Verbeeck et al, 1984). Studies reporting AAG concentrations in elderly subjects have been conflicting, i.e.…”

“…Although propranolol is bound to both albumin (ALB) and al-acid glycoprotein (AAG), the serum AAG concentration is considered to be the major factor influencing the degree of binding in a particular patient. Several studies have pointed to a direct relationship between increasing AAG concentrations and decreasing propranolol free fraction (Bendayan et al, 1984;Wallace & Verbeeck, 1987;Verbeeck et al, 1984).…”