METHYLPREDNISOLONE EXPOSURE, RATHER THAN DOSE, PREDICTS ADRENAL SUPPRESSION AND GROWTH-INHIBITION CHILDREN WITH LIVER AND RENAL-TRANSPLANTS

Some patients receiving glucocorticoids develop adverse effects even w ith very low doses, whereas others fail to achieve the desired effects with the usual therapeutic doses. We hypothesized that glucocorticoid exposure, rather than the dose, would predict the development of adve rse effects in children receiving long-term glucocorticoid treatment. Sixteen liver and 10 renal transplant recipients on triple immunosuppr ession were studied. Serum total methylprednisolone (MP) and cortisol were determined before and up to 10 h after peroral MP administration. Heights were recorded 6 months before and after the study day. The MP dose (in milligrams per kilogram) was not correlated with the serum c ortisol concentration or with the change in height SD score. The area under the serum MP time vs. concentration curve was inversely related to the serum cortisol concentration and to the height so score, and wa s the best predictor of both adrenal function and growth. Dosing accor ding to area under the serum MP time vs. concentration curve in childr en receiving long-term glucocorticoid treatment may substantially redu ce the incidence of adverse effects without affecting therapeutic effi cacy.