Alteration of plasma albumin in relation to decreased drug binding in uremia

Abstract

The binding of sulfadiazine in the plasma of normal and uremic subjects was measured by means of an ultrafiltration technique. Patients with uremia had reduced binding of sulfadiazine due to decreased albumin-binding capacity. No conclusive evidence was found to suggest that reduced drug binding in uremia is caused by competing metabolites. Studies of purified normal and uremic albumin revealed differences in amino acid composition and variations in the protein content of the two albumin bands found on isoelectric focusing. It is suggested that decreased drug binding in uremia may be at least partly due to altered albumin composition.

Haemodialysis does not affect the pharmacokinetics of nifedipine.

“…Nifedipine protein binding was not modified during haemodialysis; thereby, the decrease in protein binding was probably not a competitive interaction between drug and dialysable endogenous compounds which accummulate in uraemic patients (Andreasen, 1974;Dromgoole, 1973;Sjoholm et al, 1976). This decrease could be the consequence of an alteration of plasma albumin concentration or binding capacity (Boobis, 1977); in our study, albumin concentration in normal plasma was 39 g/l, whereas in uraemic plasma, it was respectively 26 and 30 g/l before and after haemodialysis.…”

Plasma protein binding of azapropazone in patients with kidney and liver disease.

“…warfarin site) of human serum albumin (Fehske etal., 1980 Bilirubin (mg 100ml 1) Figure 5 Free fraction values of azapropazone (0) and phenprocoumon (0) (Ghonheim & Pandya, 1975) and sulfadiazine (Boobis, 1977) while for several other drugs such correlation was apparent (Reidenberg et al, 1971;Campion, 1973;Dromgoole, 1974;O'Malley, Velasco, Pruitt & McNay, 1975;Bachmann et al, 1976;Gugler & Mueller, 1978). Several authors have suggested that the decrease in the plasma protein binding of acidic drugs in kidney disease is due to the accumulation of endogenous binding inhibitors (Craig, Evenson, Sarver & Wagnild, 1976;Sjoholm et al, 1976;OdarCederlof, 1977) which can be removed by charcoal treatment of plasma or might disappear following renal transplanation (Levy, Baliah & Procknal, 1976;Odar-Cederlof, 1977 (Fehske et al, 1980) which could explain the observed quantitative differences in the effect of disease on the binding of both drugs.…”

Plasma protein binding of furosemide in kidney transplant patients

“…Equation (1) assumes that the initial plasma and buffer volumes are equal prior to dialysis, that there is negligible binding of drug to the dialysis membrane, and that protein binding is linear. In cases of nonlinear plasma protein binding, equation (1) is inappropriate and will underestimate the true value for the percent free of drug in the original plasma sample.…”

“…It has also been established that renal impairment may alter drug binding to plasma proteins (1)(2)(3)(4)(5), particularly with respect to acidic drugs (3) include hypoalbuminemia (2), the presence of irreversible and competitive inhibitors in the plasma (3,5), and altered albumin composition (1).…”