Effect on nephrotic syndrome on absorption and disposition of prednisolone in children

The pharmacokinetics and bioavailability of prednisolone and prednisone after doses of 60 mg/m2 oral prednisone and 50 mg/m2 intravenous prednisolone were determined in six children receiving corticosteroids for treatment of nephrotic syndrome during active disease and in remission. Pharmacokinetic parameters were compared with values previously obtained from asthmatic children who received similar intravenous doses. In nephrotic children the area under the curve of prednisolone (AUCPn) was higher (by 134 +/- 42%) after oral doses of prednisone when compared to the intravenous prednisolone doses. This indicates that acute nephrotic syndrome does not produce impaired absorption and conversion of prednisone to prednisolone. A larger steady-state volume of distribution (Vss = 3.4 vs. 1.2 l/kg) was observed in active disease than in remission, suggesting greater availability of the steroid to tissues. Apparent prednisolone clearance in both stages of nephrotic syndrome were greater than those obtained in asthmatic children, possibly due to decreased protein binding of prednisolone in nephrotics. The increased tissue distribution and clearance of prednisolone which occur in children with active nephrotic syndrome decreases as their disease improves. The mean renal clearance and urinary excretion of prednisone and prednisolone in nephrotic syndrome are normal and suggest that glomerular leakage of protein bound drug is not significant.