Methylprednisolone exposure in pediatric renal transplant patients

Glucocorticoid (GC) dosing is commonly based on body mass or surface area in children, although the drug effects appear to correlate with steroid exposure, rather than dose. We compared the area under the serum concentration-time curve (AUC) of methylprednisolone (MP) with a recombinant cell bioassay measuring serum glucocorticoid bioactivity (GBA), in prediction of side effects in 16 pediatric patients (5.4-18.4 years of age) 2.0-14.9 years after renal transplantation (TX). They received 0.3 mg/kg of MP orally and timed blood samples were drawn up to 8 h postdose. Serum MP concentrations correlated moderately with GBA (r= 0.65, p < 0.0001) with best linear fit at 6 and 8 h (r= 0.72, 0.79, respectively, p < 0.001). MP-AUC(t = 0-8) and GBA(t = 6) were significantly greater in patients who gained excessive weight soon after TX. Change in growth after TX was inversely correlated with MP-AUC (r= 0.73, p < 0.05) and GBA(t = 6) (r= 0.62, p < 0.05). No correlation of MP-AUC or GBA was found with blood glucose or serum lipid concentrations, glomerular filtration rate, bone mineral density or graft histology. In conclusion, GC exposure varies individually and dosing should be adjusted accordingly to control the adverse effects. GBA might provide a complementary tool for monitoring GC exposure but further studies are needed.