REPEATED ASSESSMENT OF METHYLPREDNISOLONE PHARMACOKINETICS DURING CHRONIC IMMUNOSUPPRESSION IN RENAL-TRANSPLANT RECIPIENTS

OBJECTIVE: TO compare the pharmacokinetics of methylprednisolone in re nal transplant recipients on 2 occasions separated by at least 1 month during chronic immunosuppression. DESIGN: A prospective unblinded tri al. PATIENTS: Ten renal transplant recipients (aged 25-62 years) evalu ated in a public university-affiliate hospital clinic. INTERVENTIONS: All patients received their chronic oral dose of methylprednisolone as a 10-20-minute intravenous infusion during the 2 study periods. MAIN OUTCOME MEASURES: Serum methylprednisolone concentrations were determi ned by HPLC and were used to generate the pharmacokinetic parameters o f the drug.RESULTS: During study 1, which ranged from 1.2 to 24 months posttransplant, the mean +/- SD methylprednisolone dose was 13.2 +/- 6.4 mg. In study 2 (2.5-38.5 mo posttransplant), the mean dose was 10. 6 +/- 3 mg. During both study periods, methylprednisolone concentratio ns exhibited a monoexponential decline. Considerable variability in me thylprednisolone clearance was observed between periods in certain pat ients. Four of the 10 patients demonstrated a reduction in clearance f rom study 1 to study 2, which ranged from a 28% to a 53% decrease. Two patients exhibited an increase in clearance of 40% and 49%. The mean +/- SD total body clearance in study 1 was 363 +/- 330 mL/min/kg, wher eas the mean volume of distribution was 1.18 +/- 0.53 L/kg. The mean e limination rate constant was 0.29 +/- 0.14 h(-1), with a mean serum ha lf-life of 2.87 +/- 1.15 h during the first phase. In study 2, the mea n methylprednisolone clearance was 261 +/- 150 mL/min/kg (p > 0.05) an d the mean volume of distribution was 0.89 +/- 0.31 L/kg (p > 0.05). T he mean serum half-life of methylprednisolone was 2.91 +/- 0.60 h (p > 0.05), with the mean elimination rate constant of 0.25 +/- 0.06 h(-1) (p > 0.05). CONCLUSIONS: These data demonstrate that intrapatient var iability in methylprednisolone clearance exists among certain renal al lograft recipients. As a result of the observed variability, patients who are continued on the same dose of methylprednisolone during the po sttransplant period of chronic immunosuppression will be subjected to a changing pattern of exogenous glucocorticoid exposure. The impact of these changing patterns requires further prospective evaluation.