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)
Ohlman
S
S
Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Sweden.
Zilg
H
H
Schindel
F
F
Lindholm
A
A
D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy* / Q000378:metabolism; D006146:Guanidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus