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[Pharmacokinetics of prednisone after oral administration in children with renal grafts. Changes induced by phenobarbital and renal insufficiency].

A study of blood and urinary clearance of prednisone after ingestion of a 25 mg/m2 body surface test-dose, at 8 AM, was undertaken in 20 children treated for 18 months with prednisone after renal transplant. Results show important variability between patients: the elimination half life was 2.70 +/- 0.78 hr.; Tmax time to reach Cmax was 2.10 +/- 1.08 hr.; Maximal concentration (Cmax) was 474 +/- 153 ng/ml. With respect to the dose of steroid administered, the urinary excretion of corticosteroids: 17-hydroxycorticosteroids was 12.9 +/- 7.4% and that of unchanged prednisolone 2.8 +/- 3.1%. This level was essentially achieved in the 6 first hours: 55.4 +/- 16.2% for 17-OH steroids and 87.2 +/- 14.3% for prednisolone. Two points emerge from this study: (a) Renal failure slows urinary excretion of prednisone and its metabolites, making a reduction in the doses of corticosteroids necessary at certain doses. (b) The association prednisone-phenobarbital changes the blood kinetics (excretion is faster) without a clear change in 17-OH steroid and prednisolone urinary excretion. It is associated with a decrease in graft tolerance. The kinetic changes do not seem to be the only factors implicated in the decreased therapeutic response.