The Effect of Altered Prednisolone Kinetics in Patients with the Nephrotic Syndrome and in Women Taking Oral Contraceptive Steroids on Human Mixed Lymphocyte Cultures

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Abstract
The purpose of this study was to examine the influence of altered prednisolone kinetics in patients with the nephrotic syndrome and women taking oral contraceptive steroids on mixed lymphocyte cultures (MLC). After oral and iv prednisolone treatment, blood samples were collected over 24 h. The area under the plasma concentration us. time curve (AUC) of unbound, transcortin- bound, and albumin-bound predniso-lone was determined. All plasma samples were incubated with MLCs, and the area under the inhibition us. time curve of the MLC (AUIC), a measure of the effect over time, was calculated. The steroid concentrations required to produce half-maximal inhibition (EC50) were calculated. The 10 women taking oral contraceptives had higher AUCs of unbound and transcortin-bound prednisolone than the 10 normal subjects. The mean biological effect (AUIC value) was more pronounced in women taking contraceptive steroids. An analysis of the concentration-response curves revealed that the ECeo values of total, but not unbound, prednisolone were higher n i women taking contraceptives. Compared with the normal subjects, the 9 nephrotic patients had lower total and comparable unbound AUCs of prednisolone. The AUIC values were higher (whereas the EC50 values of unbound and total prednisolone were lower in the nephrotic patients. These findings indicate that the increased steroid effect in women taking oral contraceptives is explained by higher concentrations of prednisolone, while the increased effect in nephrotic patients is not attributable to the abnormal kinetics or protein binding of prednisolone.