Effect of age and sex on the plasma binding of acidic and basic drugs

Abstract

Protein binding of chlorpromazine, propranolol, meperidine, desipramine, salicylic acid and phenytoin was determined in plasma of 64 healthy volunteers (35 males and 29 females). An attempt was made to identify factors affecting the plasma protein binding of these drugs. Whereas plasma albumin levels decreased as a function of age in both sexes, alpha 1-acid glycoprotein levels increased with age, but the increase was more pronounced in males. The free plasma fraction of the acidic drugs (salicylic acid, phenytoin) and desipramine (a base) showed a significant (p less than 0.005) negative correlation with plasma albumin levels. The free fractions of the other three basic drugs (chlorpromazine, propranolol, meperidine) in plasma showed a significant (p less than 0.005) negative correlation with alpha 1-acid glycoprotein plasma levels. Plasma protein binding of salicylic acid, phenytoin and desipramine decreased as a function of age. Plasma protein binding of chlorpromazine, propranolol and meperidine was virtually unaffected by age or was slightly increased (chlorpromazine). Only in the case of salicylic acid could a statistically significant difference be demonstrated between males and females in the free fraction-age relationship. Stepwise multiple linear regression analysis, including age and blood chemistry values such as hematocrit, bilirubin, cholesterol, triglycerides, creatinine, BUN, albumin and alpha 1-acid glycoprotein as independent variables, identified age as the variable explaining most of the variability in plasma binding of salicylic acid, phenytoin and desipramine. For chlorpromazine, propranolol and meperidine alpha 1-acid glycoprotein was the most important determinant of plasma protein binding.

Stereoselective binding of propranolol in the elderly.

“…We were not, however, able to demonstrate any influence of age itself upon the binding of either of the propranolol enantiomers. Serum protein binding of (±)-propranolol was not statistically different in the elderly subjects, a finding which is in agreement with studies by Bendayan et al (1984) and Verbeeck et al (1984).…”

“…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).…”

The effect of age on serum concentrations of albumin and alpha 1‐acid glycoprotein.

“…The lack of effect of sex on HSA confirms (Davis et al, 1985;Verbeeck et al, 1984;Wallace et al, 1976 Davis et al (1985). Light smoking (3-10 cigarettes per day) did not distort the effect of age on HSA concentration or the lack of effect of age on AAG concentration.…”

“…Although others have suggested that AAG concentrations increase with increasing age in healthy subjects, the effect of age in these studies was small (Abernathy et al, 1984;Davis et al, 1985;Verbeeck et al, 1984) with little or no clinical consequences, as it has been shown that the plasma binding of lignocaine and pethidine is correlated significantly with AAG concentrations, but not with age (Davis et al, 1985;Herman et al, 1985).…”