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Methylprednisolone Exposure, Rather than Dose, Predicts Adrenal Suppression and Growth Inhibition in Children with Liver and Renal Transplants¹

Children’s Hospital (S.S., K.H., J.L., C.H.) and Department of Clinical Pharmacology (P.J.N.), University of Helsinki, Helsinki, Finland

Address all correspondence and requests for reprints to: Samu Sarna, Children’s Hospital, University of Helsinki, Stenbäckinkatu 11, FIN-00290, Helsinki, Finland.

Some patients receiving glucocorticoids develop adverse effects even with 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 adverse effects in children receiving long-term glucocorticoid treatment.

Sixteen liver and 10 renal transplant recipients on triple immunosuppression 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 cortisol 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 SD score, and was the best predictor of both adrenal function and growth. Dosing according to area under the serum MP time vs. concentration curve in children receiving long-term glucocorticoid treatment may substantially reduce the incidence of adverse effects without affecting therapeutic efficacy.

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