Immunosuppressive Effect of Newly Developed Tacrolimus Emulsion in Liver Transplantation
| Project/Area Number |
08671352
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
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)
|
|---|
| 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 (00092362)
|
|---|
| Project Period (FY) |
1996 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
|
|---|
| 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 / 経口用タクロリムス / o / wエマルション / 心移植 / 肝移植 / 薬物動態 |
|---|
| 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.
|
Report
(4 results)
Research Products
(6 results)
