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영어

The effects of water soluble tacrolimus-PEG conjugates (KI-102) on the insulin-dependent diabetes mellitus and systemic lupus erythematosus were investigated. The stable ranges of KI-102 were at pH 4.0-4.5 and 4℃. Area under the concentration time curve, the time of maximum concentration, and the maximum concentration were was 43.4ng.hr/mL, 0.85 hr and 8.1 ng/mL, respectively. These results were similar to those of FK506. The plasma glucose concentration in the 4.32mg/kg of KI-102-fed group at 170 days of age was decreased to 7.5 mmol/L, which was similar to that of 0.6mg/kg of FK506. There were no incidences when 86.4 mg/kg of KI-102 was administered after 24 weeks. About 60% of the β- hydroxybutyrate concentration at 43.20mg/kg-fed group, 24% of the triglyceride concentration at 43.20mg/kg-fed group, and 30% of the cholesterol concentration at 43.20mg/kg-fed group were decreased, respectively. The immunosuppressive effects of systemtic lupus erythematosus were depended on KI-102 concentration. At 180.0 mg/kg of KI-102-fed group, the serum anti-dsDNA antibody activity was about 64% of decreased compared to control. The urinary albumin concentration at 180.0 of KI-102 mg/kg-fed group was about 81% of decrease compared to that of control. These results indicate that KI-102 may be practically applicable as prodrug of FK506.