title: Effects of water-soluble tacrolimus-PEG conjugate on insulin-dependent diabetes mellitus and systemic lupus erythematosus.
abstract: The effects of a water-soluble tacrolimus-PEG conjugate (KI-102) on insulin-dependent diabetes mellitus and systemic lupus erythematosus were investigated. KI-102 was stable at pH 4.0-4.5 and 4°C. The area under the concentration-time curve, the time of maximum concentration, and the maximum concentration were 43.4 ng·h/mL, 0.85 h, and 8.1 ng/mL, respectively, similar to those of FK506. Mice that administered KI-102 at 4.32 mg/kg had the plasma glucose concentrations that decreased to 7.5 mmol/L after 170 days, similar to that of mice administered FK506 at 0.6 mg/kg. There were no incidences of diabetes when KI-102 was administered at 86.4 mg/kg after 24 weeks. The group that administered 43.2 mg/kg had decreases in the concentrations of β-hydroxybutyrate (60%), triglyceride (24%), and cholesterol (30%). KI-102 administered at 180 mg/kg reduced serum anti-dsDNA antibody activity by 64% compared with a control. Urinary albumin concentration in the same group decreased 81% compared with the control. These results indicate that KI-102 may be practically applicable as prodrug of FK506.
authors: Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
authors: DuBok
authors: D
authors: Choi
authors: Bok Hee
authors: BH
authors: Kim
authors: Myung Koo
authors: MK
authors: Lee
authors: Hoon
authors: H
authors: Cho
mesh_terms: D000284:Administration, Oral; D000418:Albumins / Q000032:analysis; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005260:Female; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
chemical_list: D000418:Albumins; D000974:Antibodies, Antinuclear; D001786:Blood Glucose; D002214:Capsules; D007166:Immunosuppressive Agents; D007328:Insulin; D011355:Prodrugs; D014280:Triglycerides; D011092:Polyethylene Glycols; D004247:DNA; D002784:Cholesterol; D016559:Tacrolimus