2002 Fiscal Year Final Research Report Summary
Pharmacokinetic and Immunosuppressive Effects of Tacrolimus-Loaded Biodegradable Microspheres
| Project/Area Number |
13671269
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Jichi Medical School (2002)
University of Shizuoka,Shizuoka College (2001) |
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Principal Investigator |
UNO Takeji Jichi Medical School, Dept of Surgery, Joshu, 医学部, 助手 (60185056)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Takaji Hamamatsu Physical and Medical Research Institute, Head, 所長
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| Project Period (FY) |
2001 – 2002
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| Keywords | tacrolimus loaded biodegradable microsphere / liver transplantation / sustained release drug delivery system / 局所免疫抑制 / ポリ乳酸グリコール酸共重合体 / ラット肝移植 / 薬物担体 |
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| Research Abstract |
Objective : To characterize the pharmacokinetics and immunosuppression of a tacrolimus loaded biodegradable microsphere (TLBM) in rats.
Methods : We prepared TLBM. DA/Slc rats were given TLBM at a rate of 1.6 mg/kg (n=9), 2.4 mg/kg (n=5), and 7.2 mg/kg (n=7) tacrolimus contents, respectively, by a single subcutaneous administration to achieve sustained release over a long period. DA/Slc rats were given TLBM by a single subcutaneous administration at a rate of 4.8 mg/kg (n=6) tacrolimus contents to clarify the main site of TLBM uptake in the organs. In the rat liver transplantation model, the recipients were given TLBM at a rate of 0.16 mg/kg (n=5), 2.4 mg/kg (n=4), and 4.8 mg/kg (n=3) tacrolimus contents, respectively by a single subcutaneous administration on the first day postoperation. Overall survival days were compared.
Results : The mean diameters of TLBM particles were 87-90 μm. The entrapping efficiencies of tacrolimus in two batches of TLBM were 6.48 w/w% and 6.60 w/w%. Continuous flat parallel concentration profiles were significant for 14 days from the first day after a single subcutaneous administration of TLBM (p<0.01). The relationship between the dosages of TLBM administration and area under the concentration-time curve (AUC) up to 18 days demonstrated a linear regression line (p<0.01). Also, the relationship between the dose of TLBM and the survival days of the recipients in the liver transplantation model showed a positive correlation. The present pharmacokinetic study of TLBM revealed significantly increased tacrolimus levels in the regional lymph nodes, compared with other organs except bone marrow (p<0.01).
Conclusion : TLBM allowed tacrolimus to release gradually in a very stable manner for 14 days and revealed dose proportionality and dose-dependent immunosuppression after a single subcutaneous administration. The main site of TLBM uptake after subcutaneous administration was the regional lymph node of administration route.
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Research Products
(1 results)
