COMPARATIVE METHYLPREDNISOLONE PHARMACOKINETICS IN RENAL-TRANSPLANT PATIENTS RECEIVING DOUBLE-DRUG OR TRIPLE-DRUG IMMUNOSUPPRESSION

OBJECTIVE: To assess the pharmacokinetics of chronic methylprednisolon e therapy in renal transplant patients receiving double-drug (methylpr ednisolone and azathioprine) and triple-drug (methylprednisolone, azat hioprine, and cyclosporine) immunosuppression. DESIGN: Parallel, rando mized trial. PATIENTS: Fourteen renal transplant recipients (aged 29-6 5 y) evaluated in a public, university-affiliated hospital clinic. INT ERVENTIONS: All patients received their chronic oral dose of methylpre dnisolone via a 10-20-minute intravenous infusion. MAIN OUTCOME MEASUR ES: Serum methylprednisolone concentrations were determined by HPLC an d were used to generate pharmacokinetic parameters for this drug. RESU LTS: The mean daily methylprednisolone dosage was 19 +/- 19 mg in the double-drug group and 9 +/- 2 mg in the triple-drug group. Mean serum creatinine concentrations were 124 +/- 44 and 124 +/- 27 mumol/L, resp ectively. Mean methylprednisolone clearances were similar in both grou ps: 405 +/- 205 (double-drug) and 373 +/- 365 mL/h/kg (triple-drug) (p >0.05). Mean steady-state volume of distribution was 1.5 +/- 0.8 L/kg in the double-drug group and 1.3 +/-0.8 L/kg in the triple-drug group (p>0.05). Plasma half-life ranged from 1.7 to 4.3 h (mean 2.7) in the double-drug group versus 1.4 to 3.4 h (mean 2.6) in the triple-drug gr oup (p>0.05). CONCLUSIONS: These data indicate that cyclosporine had n o definitive influence on methylprednisolone disposition. The results reveal a wide variation in methylprednisolone metabolism in renal tran splant recipients receiving either a double- or triple-drug immunosupp ressive regimen. Typically, methylprednisolone is prescribed according to a standardized dosing protocol that assumes minimal interpatient v ariation. Therefore, the pharmacokinetic variability noted in this stu dy may have important clinical implications regarding the development of chronic toxicity (e.g., osteoporosis, hypothalamic-pituitary-adrena l suppression) and the attainment of successful immunosuppression.