2003 Fiscal Year Final Research Report Summary
optimal immunosuppression after organ transplantation from the view point of CYP3A activity
Project/Area Number |
14571157
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
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Research Institution | KEIO UNIVERSITY |
Principal Investigator |
HOSHINO Ken KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 専任講師 (70190197)
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Co-Investigator(Kenkyū-buntansha) |
TANABE Minoru KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (50197513)
MORIKAWA Yasuhide KEIO UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (90124958)
MORITA Kunihiko KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80327717)
SHIMOJIMA Naoki KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT, 医学部, 助手 (30317151)
WATANABE Roshihiko KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT (50306734)
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Project Period (FY) |
2002 – 2003
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Keywords | liver transplantation / CYP3A activity / 6B-hydroxycortisol / cyclosporin / marker of rejection / metabolites of cyclosporin / GB-OHF / F ratio / acute cellular rejection |
Research Abstract |
To elucidate relationship between CYP3A activity and disposition of cyclosporin A (CyA) after living donor liver transplantation (LDLT), the blood concentrations of CyA and its metabolites by monoclonal specific and polyclonal non-specific FPIA methods were determined in LDLT patients (mean age ± S.E., 1.7±1.0). Blood concentrations of CyA metabolites (mainly 1-hydroxy metabolite) began to increase at post-operative day-1 and they reached steady-state at postoperative day-4. CYP3A activity could maintain even early period after liver transplantation. On the other hand, the ratio of urinary 6B-hydroxycortisol / cortisol (6B-OHF/F), a noninvasive maker of CYP3A activity, in LDLT patients increased 2 to 10-fold to its normal levels at about 1 or 2 days before episode of rejection. In conclusions, the results suggest that CYP3A in the graft liver already has a normal activity in earliest stage after the operation and the ratio of urinary 6B-OHF/F might utilize to predict episode of rejection.
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