Age- and gender-related differences in carbohydrate concentrations of α 1 -acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities

Abstract

The mean plasma AAG concentration in the female subjects was significantly lower than that in the male subjects (0.67 +/- 0.12 mg/ml, mean +/- SD, in females, n = 15, versus 0.81 +/- 0.17 mg/ml in males, n = 17, P < 0.05), but no age-related differences were found (0.75 +/- 0.18 mg/ml in young subjects, n = 24, versus 0.77 +/- 0.12 mg/ml in older subjects, n = 8, n.s.). However, the degree of branching of the glycan chain in the female subjects was significantly lower than that in the male subjects (1.61 +/- 0.17 mol/mol, mean +/- SD, in females, n = 15, versus 1.75 +/- 0.23 mol/mol in males, n = 17, P < 0.05). There was a significant inverse relationship between the binding capacity of AAG to DP (Cb/AAG) and the degree of branching of the glycan chain. The binding capacity (Cb/AAG) decreased as the degree of branching in AAG glycans increased. The binding capacity (Cb/AAG) in the female subjects was significantly higher than that in the male subjects (2.79 +/- 0.59 mg/g AAG in females, mean +/- SD, n = 15, versus 2.37 +/- 0.29 mg/g AAG in males, n = 17, P < 0.05). CONCLUSION. The degree of branching of the glycan chain in AAG plays an important role in drug-binding capacity. Gender-related differences in drug-binding capacity (Cb/AAG) may be caused by differences in the ratios of the extent of branching of the glycan chain in AAG.

Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities

“…AGP is capable of binding methadone and rendering it inactive (45). In general, females have a significantly greater binding capacity of AGP than males, suggesting that females could have a reduced level of free plasma drug levels (46). In this study, there were no significant differences in the blood methadone concentration or the [methadone]/[EDDP] ratio between the male and female groups for any of the SNPs tested (data not shown).…”

Correlation of blood-brain penetration and human serum albumin binding with theoretical descriptors

“…Under various physiological and pathological conditions the amount of plasma proteins in blood might be decreased and for strongly bound drugs there could be risk of enhanced activity and undesirable side effects. [12][13] Human serum albumin (HSA), a single monomeric polypeptide of 585 amino acidic residues, is the most abundant soluble protein in human serum, with a typical concentration of 0.6 mM in the bloodstream 14 contributing significantly to the colloidal oncotic pressure and antioxidative capacity of human serum. 15,16 Furthermore, HSA has a remarkable ability to bind, non-covalently, a wide range of chemically diverse endogenous (fatty acids, metabolites) and exogenous ligands.…”

Stability, pKa and plasma protein binding of roscovitine

“…Thus, changes in plasma binding may alter the drug pharmacokinetics and consequently its pharmacological effect. In this context, the ratio of unbound/bound drug in plasma has been described to differ in renal, liver, neoplastic diseases, pregnancy and age [3,9,[11][12][13].…”

“…It has been reported the concentration of albumin varies in relation to age, pregnancy, stress, renal and hepatic diseases, malnutrition and cancer. ␣1-AGP levels have been shown to be affected in liver dysfunction, neoplastic diseases, infections, rheumatoid arthritis, age, pregnancy and burns (for review, see [9][10][11][12]). Changes in lipoprotein concentrations have not been extensively documented, though variations of these proteins has been observed in hyperproteinlipidemias [9].…”