Comparative methylprednisolone pharmacokinetics in renal transplant patients receiving double- or triple-drug immunosuppression.

OBJECTIVE

To assess the pharmacokinetics of chronic methylprednisolone therapy in renal transplant patients receiving double-drug (methylprednisolone and azathioprine) and triple-drug (methylprednisolone, azathioprine, and cyclosporine) immunosuppression.

DESIGN

Parallel, randomized trial.

PATIENTS

Fourteen renal transplant recipients (aged 29-65 y) evaluated in a public, university-affiliated hospital clinic.

INTERVENTIONS

All patients received their chronic oral dose of methylprednisolone via a 10-20-minute intravenous infusion.

MAIN OUTCOME MEASURES

Serum methylprednisolone concentrations were determined by HPLC and were used to generate pharmacokinetic parameters for this drug.

RESULTS

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, respectively. Mean methylprednisolone clearances were similar in both groups: 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 group (p > 0.05).

CONCLUSIONS

These data indicate that cyclosporine had no definitive influence on methylprednisolone disposition. The results reveal a wide variation in methylprednisolone metabolism in renal transplant recipients receiving either a double- or triple-drug immunosuppressive regimen. Typically, methylprednisolone is prescribed according to a standardized dosing protocol that assumes minimal interpatient variation. Therefore, the pharmacokinetic variability noted in this study may have important clinical implications regarding the development of chronic toxicity (e.g., osteoporosis, hypothalamic-pituitary-adrenal suppression) and the attainment of successful immunosuppression.