Summary
The protein binding of prednisolone was studied in plasma obtained from healthy volunteers in the presence of added amounts of prednisone and hydrocortisone. The plasma protein binding was determined using in vitro equilibrium dialysis for 16 h at 37°C against isotonic Krebs-Ringer buffer using radioactive prednisolone. Prednisone appeared to have no effect on prednisolone binding. This surprising result was observed even when prednisone concentrations were more than 35 fold greater than prednisolone concentrations. In contrast, a marked competition between hydrocortisone and prednisolone was observed. These binding data were fit using a nonlinear least squares regression computer program and the capacity and affinity constants for the binding of prednisolone to transcortin and albumin were estimated including the competition for binding sites between prednisolone and hydrocortisone. The results from these studies compare favorably with recent parameter calculations, and our previous work where differences in binding were noted between cushingoid and noncushingoid patients.
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Frey FJ, Frey BM, Benet LZ (1979) Liquid-chromatographic measurements of endogenous and exogenous glucocorticoids in plasma. Clin Chem 25: 1944–1947
Legler UF, Frey FJ, Benet LZ (1982) Prednisolone clearance at steady state in man. J Clin Endocrinol Metab 55: 762–767
Lewis GP, Jusko WJ, Burke CW, Graves L (1971) Prednisolone side-effects and serum protein levels. Lancet 2: 778
Chen PS, Mills IH, Bartter FC (1961) Ultrafiltration studies of steroid-protein binding. J Endocrinol 23: 129
Rocci ML, Ambrosio D, Johnson R, Jusko WJ (1982) Prednisolone binding to albumin and transcortin in the presence of cortisol. Biochem Pharmacol 31: 289–292
Behm HL, Wagner JG (1979) Errors in interpretation of data from equilibrium dialysis protein binding experiments. Res Commun Chem Pathol Pharmacol 26: 145–160
Tozer TN, Gambertoglio JG, Furst DE, Avery D, Holford NHG (1983) Volume shifts during equilibrium dialysis and protein binding estimates — application to prednisolone binding in man. J Pharm Sci 72: 1442–1446
Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672
Pegg PJ, Keane PM (1969) The simultaneous estimation of plasma cortisol and transcortin binding characteristics by a competitive protein binding technique. Steroids 14: 705
MULTIFUN (1974) A biomathematical modelling procedure available on the NIH sponsored PROPHET computing system. Proc Nat Computer Conf Expos 43: 457
Westphal U (1969) Corticoid-binding globulin and other steroid-binding serum proteins. In: Clayton RB (ed) Methods in enzymology, XV. Steroids and terpenoids. Academic Press, New York, pp 761–796
Agabeyoglu IT, Bergstrom WR, Gillespie WR, Wagner JG, Kay DR (1979) Plasma protein binding of prednisolone in normal volunteers and arthritic patients. Eur J Clin Pharmacol 16: 399–404
Rose JQ, Nickelsen JA, Middleton E, Yurchak AM, Park BH, Jusko WJ (1980) Prednisolone disposition in steroid-dependent asthmatics. J Allergy Clin Immunol 66: 366–373
Frey FJ, Amend WJC, Lozada F, Frey BM, Holford NHG, Benet LZ (1981) Pharmacokinetics of prednisolone and endogenous hydrocortisone levels in cushingoid and noncushingoid patients. Eur J Clin Pharmacol 21: 235–242
Frey FJ, Amend WJC, Lozada F, Frey BM, Benet LZ (1981) Endogenous hydrocortisone, a possible factor contributing to the genesis of cushingoid habitus in patients on prednisone. J Clin Endocrinol Metab 53: 1076–1080
Benet LZ, Frey FJ, Amend WJC, Lozada F, Frey BM (1982) Endogenous and exogenous glucocorticoids in cushingoid patients. Drug Intell Clin Pharm 16: 863–868
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Legler, U.F., Benet, L.Z. The effect of prednisone and hydrocortisone on the plasma protein binding of prednisolone in man. Eur J Clin Pharmacol 30, 51–55 (1986). https://doi.org/10.1007/BF00614195
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DOI: https://doi.org/10.1007/BF00614195