[Pharmacokinetics of prednisolone in children. Study of a correlation with tolerability and therapeutic effect in nephrosis]

In patients with nephrotic syndrome the response to corticosteroids and the way these drugs are tolerated are extremely variable. The purpose of this study was to investigate possible correlations between the pharmacokinetic values of prednisolone and the main clinical criteria of effectiveness and safety. The study was performed on 18 children under corticosteroid therapy: 16 with nephrotic syndrome and 2 with a systemic disease. Measurements were performed by radiocompetition with transcortine after an oral dose of 1 mg/kg bodyweight. Pharmacokinetic values varied considerably, with peak plasma levels ranging from 1.2 to 6.1 micrograms/ml between 20 and 120 minutes, and T 1/2 values of 77 to 648 minutes. Within this scattering of values, some patients were clearly outside the mean T 1/2 value (3.1 +/- 1 hours) due to a particularly fast or slow metabolisation of the drug. In patients with nephrotic syndrome no correlation was found between pharmacokinetic values and criteria of clinical effectiveness, such as the time and dosage required to obtain remissions and the duration of these remissions. Hypoalbuminaemia had no influence on the metabolism of prednisolone. In contrast, there was a correlation between pharmacokinetic values and side-effects, since patients who presented with side-effects also had a significantly greater area under plasma concentration versus time curves. This pharmacokinetic test may be used when corticosteroids produce unusual or unexplainable therapeutic results or adverse reactions.