Cyclosporine a-based immunotherapy in adult living donor liver transplantation: Accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion

Taizo Hibi, Minoru Tanabe, Ken Hoshino, Yasushi Fuchimoto, Shigeyuki Kawachi, Osamu Itano, Hideaki Obara, Masahiro Shinoda, Naoki Shimojima, Kentaro Matsubara, Yasuhide Morikawa, Yuukou Kitagawa

Research output: Contribution to journalArticle

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Abstract

Background: A paucity of data exists for evaluating therapeutic drug monitoring in association with clinical outcomes of cyclosporine A (CYA) treatment in living donor liver transplantation (LDLT). Methods: A retrospective cohort analysis was conducted on 50 consecutive adult patients who underwent LDLT between 2001 and 2009 to investigate the feasibility and efficacy of 4-hr continuous intravenous infusion of CYA-based immunotherapy (4-hr CYA-IV, n=27) and compare the pharmacokinetic profile and short-term prognoses with an oral microemulsion formulation of CYA (CYA-ME, n=23). Results: All patients in the 4-hr CYA-IV group reached target CYA peak by day 3 compared with only 22% in the CYA-ME group (P<0.001). Adjustability to achieve the target range was easier in the 4-hr CYA-IV group compared with the CYA-ME group (P=0.017). Acute cellular rejection rate was lower in the 4-hr CYA-IV group (0%) compared with the CYA-ME group (17%, P=0.038). A subset analysis of the CYA-ME group revealed that CYA exposure was affected by external bile output (P=0.006). Patients in the CYA-ME group showed increased risk of switch to tacrolimus (35%) compared with the 4-hr CYA-IV group (7%, P=0.030). Toxicities and mortality rates were equivalent. The optimal initial dose of oral CYA at conversion from the 4-hr CYA-IV was considered to be 3-fold greater than that of the intravenous dose. Conclusions: In LDLT, our 4-hr CYA-IV immunosuppression protocol was superior to CYA-ME oral dosing and allowed accurate therapeutic drug monitoring with excellent patient compliance.

Original languageEnglish
Pages (from-to)100-105
Number of pages6
JournalTransplantation
Volume92
Issue number1
DOIs
Publication statusPublished - 2011 Jul 15

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Drug Monitoring
Living Donors
Intravenous Infusions
Liver Transplantation
Immunotherapy
Cyclosporine

Keywords

  • Cyclosporine A
  • Immunosuppression
  • Living donor liver transplantation
  • Rejection
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Transplantation

Cite this

Cyclosporine a-based immunotherapy in adult living donor liver transplantation : Accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion. / Hibi, Taizo; Tanabe, Minoru; Hoshino, Ken; Fuchimoto, Yasushi; Kawachi, Shigeyuki; Itano, Osamu; Obara, Hideaki; Shinoda, Masahiro; Shimojima, Naoki; Matsubara, Kentaro; Morikawa, Yasuhide; Kitagawa, Yuukou.

In: Transplantation, Vol. 92, No. 1, 15.07.2011, p. 100-105.

Research output: Contribution to journalArticle

Hibi, Taizo ; Tanabe, Minoru ; Hoshino, Ken ; Fuchimoto, Yasushi ; Kawachi, Shigeyuki ; Itano, Osamu ; Obara, Hideaki ; Shinoda, Masahiro ; Shimojima, Naoki ; Matsubara, Kentaro ; Morikawa, Yasuhide ; Kitagawa, Yuukou. / Cyclosporine a-based immunotherapy in adult living donor liver transplantation : Accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion. In: Transplantation. 2011 ; Vol. 92, No. 1. pp. 100-105.
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abstract = "Background: A paucity of data exists for evaluating therapeutic drug monitoring in association with clinical outcomes of cyclosporine A (CYA) treatment in living donor liver transplantation (LDLT). Methods: A retrospective cohort analysis was conducted on 50 consecutive adult patients who underwent LDLT between 2001 and 2009 to investigate the feasibility and efficacy of 4-hr continuous intravenous infusion of CYA-based immunotherapy (4-hr CYA-IV, n=27) and compare the pharmacokinetic profile and short-term prognoses with an oral microemulsion formulation of CYA (CYA-ME, n=23). Results: All patients in the 4-hr CYA-IV group reached target CYA peak by day 3 compared with only 22{\%} in the CYA-ME group (P<0.001). Adjustability to achieve the target range was easier in the 4-hr CYA-IV group compared with the CYA-ME group (P=0.017). Acute cellular rejection rate was lower in the 4-hr CYA-IV group (0{\%}) compared with the CYA-ME group (17{\%}, P=0.038). A subset analysis of the CYA-ME group revealed that CYA exposure was affected by external bile output (P=0.006). Patients in the CYA-ME group showed increased risk of switch to tacrolimus (35{\%}) compared with the 4-hr CYA-IV group (7{\%}, P=0.030). Toxicities and mortality rates were equivalent. The optimal initial dose of oral CYA at conversion from the 4-hr CYA-IV was considered to be 3-fold greater than that of the intravenous dose. Conclusions: In LDLT, our 4-hr CYA-IV immunosuppression protocol was superior to CYA-ME oral dosing and allowed accurate therapeutic drug monitoring with excellent patient compliance.",
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AU - Hibi, Taizo

AU - Tanabe, Minoru

AU - Hoshino, Ken

AU - Fuchimoto, Yasushi

AU - Kawachi, Shigeyuki

AU - Itano, Osamu

AU - Obara, Hideaki

AU - Shinoda, Masahiro

AU - Shimojima, Naoki

AU - Matsubara, Kentaro

AU - Morikawa, Yasuhide

AU - Kitagawa, Yuukou

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AB - Background: A paucity of data exists for evaluating therapeutic drug monitoring in association with clinical outcomes of cyclosporine A (CYA) treatment in living donor liver transplantation (LDLT). Methods: A retrospective cohort analysis was conducted on 50 consecutive adult patients who underwent LDLT between 2001 and 2009 to investigate the feasibility and efficacy of 4-hr continuous intravenous infusion of CYA-based immunotherapy (4-hr CYA-IV, n=27) and compare the pharmacokinetic profile and short-term prognoses with an oral microemulsion formulation of CYA (CYA-ME, n=23). Results: All patients in the 4-hr CYA-IV group reached target CYA peak by day 3 compared with only 22% in the CYA-ME group (P<0.001). Adjustability to achieve the target range was easier in the 4-hr CYA-IV group compared with the CYA-ME group (P=0.017). Acute cellular rejection rate was lower in the 4-hr CYA-IV group (0%) compared with the CYA-ME group (17%, P=0.038). A subset analysis of the CYA-ME group revealed that CYA exposure was affected by external bile output (P=0.006). Patients in the CYA-ME group showed increased risk of switch to tacrolimus (35%) compared with the 4-hr CYA-IV group (7%, P=0.030). Toxicities and mortality rates were equivalent. The optimal initial dose of oral CYA at conversion from the 4-hr CYA-IV was considered to be 3-fold greater than that of the intravenous dose. Conclusions: In LDLT, our 4-hr CYA-IV immunosuppression protocol was superior to CYA-ME oral dosing and allowed accurate therapeutic drug monitoring with excellent patient compliance.

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KW - Rejection

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