The effect of ageing on plasma albumin and plasma protein binding of diazepam, salicylic acid and digitoxin in healthy subjects and patients with renal impairment.

Abstract

1. Plasma albumin concentration was measured in 118 healthy subjects (aged between 18 and 87 years), in 95 renal patients with creatinine clearances between 15 and 50 ml min‐1 (aged between 14 and 79 years) and in 101 uraemic patients maintained on chronic haemodialysis (aged between 27 and 83 years). 2. There was a significant (P less than 0.001) negative correlation between albumin concentration and age in healthy subjects, but no correlation in patients with low creatinine clearance or in uraemic patients. 3. The ex vivo plasma binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (37 nM) was studied in groups of age‐selected young and aged healthy subjects in patients with low creatinine clearance and in patients with uraemia. The unbound fractions of diazepam and salicylic acid were about double in old compared with young healthy subjects whereas they were similar in young and old patients with lowered creatinine clearance. In uraemic patients, ageing did not affect the binding of salicylic acid whereas the unbound fraction of diazepam was slightly but significantly greater in elderly subjects. The unbound fraction of digitoxin was independent of age in both healthy subjects and in those with renal disease. 4. Decreased plasma binding of diazepam and salicylic acid was partially corrected by extensive dialysis of plasma. The lower plasma binding of diazepam and salicylic acid associated with ageing may be ascribed to the effects of endogenous displacers and to hypoalbuminaemia. The influence of these two factors appears to be drug‐dependent.

Inhibition of Sulfotransferases by Xenobiotics

“…The IC 50 s for salicylic acid of (HUMAN)SULT1A1 in the adult and fetal livers are 25-30 µM ( Table 6), whereas the therapeutic concentrations of salicylic acid range between 1100 µM and 2200 µM [138]. When corrected for the unbound plasma (19.6%) [139], the values are 210 µM and 430 µM. This suggests that salicylic acid concentration after therapeutic doses of acetylsalicylic acid may be high enough to inhibit sulfonation of (-)-salbutamol and (-)-apomorphine in vivo [133].…”

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

“…An excellent correlation was demonstrated between saliva melatonin in humans and levels of unbound serum melatonin, suggesting for the first time that melatonin binding to plasma proteins may affect the levels of free melatonin and hence physiological responses (Kennaway and Voultsios, 1998). Because the levels of albumin and ␣1-acid glycoprotein may vary with age and disease, particularly during inflammatory processes, the level of free melatonin and drugs in human plasma cannot be predicted and has to be considered on a case-by-case basis (Viani et al, 1992;Morin et al, 1997;Waldhauser et al, 1988).…”

Anticoagulant-induced changes on antibiotic concentrations in the serum and bones

“…This depends on the drug's pharmacological properties among which protein binding plays a significant role and the extent of its binding capacity is influenced by various factors (29)(30)(31)(32)(33)(34)(35)(36)(37)(38).…”