PHARMACOKINETICS OF METHYLPREDNISOLONE DURING ACUTE RENAL-ALLOGRAFT REJECTION

High dose methylprednisolone is administered empirically by fixed dail y blouses to renal transplant recipients who are experiencing acute re jection episodes, Little information is available characterizing the p harmacokinetics of high-dose methylprednisolone in these individuals, who are often acutely ill, Therefore, 5 renal transplant recipients (2 men; 3 women) were studied during Bn acute rejection episode (mean se rum creatinine=2.6+/-0.7 mg/dl) which occurred within the first 8 mont hs posttransplantation. The rejection episode was characterized clinic ally by at least two of the following: fever, leukocytosis, graft tend erness and an increase in serum creatinine. All patients received bolu s doses of methylprednisolone for 3 consecutive days during the reject ion episode. All patients were studied on the 3rd day of bolus dosing and received 250 mg methylprednisolone by an i.v. infusion. In phase I I, 4 patients were studied during a period of stable renal function wh en the methylprednisolone was given at lower chronic immunosuppressive doses. Serum samples were taken prior to infusion and serially over t he following 24 hours. The serum samples were analyzed for methylpredn isolone with high-performance liquid chromatography (HPLC) and pharmac okinetic parametes were generated. During rejection episodes, the meth ylprednisolone clearance values were 523+/-154 ml/h/kg with a correspo nding mean volume of distribution of 1.89+/-0.,72 l/kg. The mean methy lprednisolone half-life was 2.61+/-0.62 h. During Phase II, the methyl prednisolone clearance was 358+/-95 ml/h/kg with a half-life of 3.05 h . This observation indicates that methylprednisolone metabolism is inc reased during acute rejection compared to that seen during chronic imm unosuppressive dosing with this agent.