Pharmacokinetics of 15-deoxyspergualin studied in renal transplant patients receiving the drug during graft rejection.

The pharmacokinetics of the novel immunosuppressant 15-deoxyspergualin (DSG) were studied in five renal transplant patients who participated in a dose-finding study for the treatment of renal graft rejection. DSG, in a dose of 4 or 6 mg/kg per day, was given in a 3-h i.v. infusion for 5 days, in combination with a 4-day course of i.v. methylprednisolone. Analyses of DSG in plasma and urine were performed by high-performance liquid chromatography (HPLC). Plasma samples were taken up to 12 h following infusion on treatment day 2 and again on day 4 or 5. Urine was collected during the infusion and up to 12 h following the infusion. DSG was rapidly eliminated from the plasma in an apparently biexponential manner. The mean t1/2 alpha was 0.5 h (range 0.1-1.1 h) and the mean t1/2 beta 2.4 h (range 1.0-5.9 h). The mean Cmax was 4117 ng/ml (range 1944-7166 ng/ml) and the mean AUC 12505 ng.ml-1 x h (range 5642-24436 ng.ml-1 x h). Clearance ranged from 375 to 945 ml/min (mean 653 ml/min) and volume of distribution ranged from 0.2 to 1.4 l/kg (mean 0.7 l/kg). A small fraction (mean 1.6%, range 0.1%-2.7%) of the DSG dose given was excreted unmetabolized in the urine. The amount of DSG in the urine correlated strongly to renal function (P = 0.0019). Pharmacokinetics were otherwise not affected by the degree of renal function. There were no significant differences in the pharmacokinetic determinants and no accumulation of the drug on study day 4 or 5, as compared to day 2.(ABSTRACT TRUNCATED AT 250 WORDS)