1998 Fiscal Year Final Research Report Summary
Immunosuppressive Effect of Newly Developed Tacrolimus Emulsion in Liver Transplantation
| Project/Area Number |
08671352
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
UNO Takeji Hamamatsu University School of Medicine, First Department of Surgery, Assistant Professor, 医学部附属病院, 講師 (60185056)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Hisakuni Hamamatsu University School of Medicine, Professor, 医学部附属病院, 教授 (10009558)
YAMAGUCHI Takaji Hamamatsu Physical and Medical Research Institute, the head, 所長
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| Project Period (FY) |
1996 – 1998
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| Keywords | Tacrolimus / Water-in-Oil-in-Water-Type Multiple Emulsion / Oil-in-Water-Type Emulsion / Immunosuppressive effect / Wエマルション / ラット心移植 / ラット肝移植 / 急性移植片対宿主病治療 |
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| Research Abstract |
1. We developed an oleic acid oil-in-water(o/w)-type emulsion of a new tacrolimus formulation that represented an improvement in the delivery of the drug for oral absorption. The whole blood concentration profiles after oral administration at dose of 2mg/kg and bone marrow, spleen, liver, lung, small intestine, kidney, brain, and whole blood distribution after oral administration at dose of 1mg/kg of o/w emulsion formulation of tacrolimus (O/W group) were compared with those of commercially available formulation (T group) in the rat. The mean diameters of the olw emulsion droplets were 0.47 mu m immediately after it's preparation. The tacrolimus entrapping efficiency of o/w emulsion was 71.3 5.0% in 12 hrs and did not change for 2 days. The value of area under the whole blood concentration- time curve in the 0/W group was significantly higher (p<0.01) than that in the T group. In contrast, the values of constant elimination rate and total clearance in the O/W group were significantly lower (p<0.01) than those in the T group. The value of comparative bioavailability was 115.9%. The tissue concentration values of tacrolimus in the O/W group demonstrated significantly increased levels in the bone marrow, spleen, liver, lung, and small intestine, and significantly decreased levels in the brain and kidney, relative to the T group.
2. We investigated the immunosuppressive effects of tacrolimus o/w emulsion in rat cardiac allografts and liver allografts. It has found that the oral administration of tacrolimus o/w emulsion is not more effective in prolonging survival of cardiac and liver allografts in rats, relative to the commercially available formulation.
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Research Products
(4 results)
