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2003 Fiscal Year Final Research Report Summary

optimal immunosuppression after organ transplantation from the view point of CYP3A activity

Research Project

Project/Area Number 14571157
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKEIO UNIVERSITY

Principal Investigator

HOSHINO Ken  KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 専任講師 (70190197)

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)
Project Period (FY) 2002 – 2003
Keywordsliver 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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Published: 2005-04-19  

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