The binding of prednisolone in human serum and to recrystallized human albumin in vitro.

Abstract

1 Prednisolone binding in human serum and to recrystallized human serum albumin was measured by continuous ultrafiltration. 2 At serum concentrations of prednisolone up to 0.6 micron, 95.0% was bound but at higher concentrations the binding became non‐linear falling to 80.5% at 1.8 microns. At even higher concentrations binding in serum became linear again and paralleled the binding to albumin which was linear throughout the entire range of prednisolone concentrations. 3 A binding model was proposed which included a saturable component attributable to binding to transcortin and a non‐saturable binding to albumin. 4 Computer simulations using the experimentally determined binding parameters of the model indicated that binding in serum was critically dependent on transcortin concentration and almost independent of albumin concentration.

Pharmacokinetics of prednisone and its metabolite prednisolone in children with nephrotic syndrome during the active phase and in remission.

“…This phenomenon is related to saturation of the high affinity-low capacity binding to transcortin, while the binding to albumin shows low affinity and high capacity and appears to be largely concentration independent (Lewis et al, 1971;Wagner et al, 1981;Steele et al, 1982). The mechanism responsible for the marked impairment of prednisolone binding capacity in the acute phase of the nephrotic syndrome remains to be established.…”

“…Our finding of a significant negative correlation between albumin concentration and free prednisolone fraction during acute disease does not prove a cause-effect relationship. Transcortin, for example, has been considered in some studies as a more important determinant of changes in prednisolone binding (Frey & Frey, 1982b;Steele et al, 1982) and is known to decrease in nephrotic patients in a parallel fashion with the fall in plasma albumin (Frey & Frey, 1982a). The possible role of endogenous binding inhibitors should also be considered.…”

Pharmacokinetics of prednisolone in children with nephrosis.

“…Their median age was 10 years (range [4][5][6][7][8][9][10][11][12][13][14][15][16] and their median plasma albumin concentration was 23 g/l (range: 16-33 g/l) (table 1). Prednisolone was given as an intravenous bolus injection of prednisolone phosphate (Codelsol; Merk, Sharpe and Dohme) 30-64 mg (median: 60 mg).…”

Biowaiver Monographs for Immediate Release Solid OralDosage Forms: Prednisolone

“…The fraction bound is not constant and decreases in a nonlinear fashion with increasing concentrations: at low concentrations protein binding appears to be quite high (80%-90%), but declines at higher prednisolone levels to 60%-70%. [33], [44], [49], [50], [52] For plasma concentrations of up to 400 ng/mL an approximate linear function of fraction bound can be assumed, which switches over to a constant (lower) relation above 600 ng/mL, [44] reflecting the saturable binding of prednisolone to transcortin. Binding of prednisolone to plasma protein is independent of the route of administration.…”