METHYLPREDNISOLONE-HEMISUCCINATE AND ITS METABOLITES IN SERUM, URINE AND BILE FROM 2 PATIENTS WITH ACUTE GRAFT-REJECTION

Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-a lpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (2 0 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h in travenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patien ts with rheumatoid arthritis (historical controls) who had normal live r function. The transplant patients showed a ratio in urine of 'total metabolites'/MPHS that was one third that of patients with rheumatoid arthritis. Less than 0.2% of the administered MPHS appeared in bile as MPHS, MP, 20 alpha HMP and 20 beta HMP during the 24 h following infu sion. Liver transplantation did not affect the overall elimination of drug in urine. However, the impaired liver function following transpla ntation resulted in reduced conversion of MPHS to its active form (MP) .