Analysis of the variable factors influencing tacrolimus blood concentration during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation

Kimitaka Suetsugu, Hiroaki Ikesue, Toshihiro Miyamoto, Motoaki Shiratsuchi, Nanae Yamamoto-Taguchi, Yuichi Tsuchiya, Kumi Matsukawa, Mayako Uchida, Hiroyuki Watanabe, Koichi Akashi, Satohiro Masuda

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Abstract

The aim of this retrospective study was to identify variable factors affecting tacrolimus blood concentration during the switch from continuous intravenous infusion to twice-daily oral administration in allogeneic hematopoietic stem cell transplant recipients (n = 73). The blood concentration/dose ratio of tacrolimus immediately before the change from continuous infusion (C/Div) was compared with that between 3 and 5 days after the change to oral administration (C/Dpo). Median (C/Dpo)/(C/Div) was 0.21 (range 0.04–0.58). Multiple regression analysis showed that concomitant use of oral itraconazole or voriconazole significantly increased the (C/Dpo)/(C/Div) of tacrolimus (p = 0.002), probably owing to the inhibition of enterohepatic cytochrome P450 3A4. In addition, 5 of 18 (28%) patients who had the lowest quartile (C/Dpo)/(C/Div) values developed acute graft-versus-host-disease (GVHD), which was significantly higher than in others [5 of 55 (9%) patients, p = 0.045]. Although the switch from intravenous to oral administration at a ratio of 1:5 appeared to be appropriate, a lower conversion ratio was suitable in patients taking oral itraconazole or voriconazole. In patients whose blood concentration decreases after the switch, the development of GVHD should be monitored and tacrolimus dosage should be readjusted to maintain an appropriate blood concentration.

Original languageEnglish
Pages (from-to)361-368
Number of pages8
JournalInternational Journal of Hematology
Volume105
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

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Hematopoietic Stem Cell Transplantation
Tacrolimus
Intravenous Infusions
Statistical Factor Analysis
Oral Administration
Itraconazole
Graft vs Host Disease
Cytochrome P-450 CYP3A
Hematopoietic Stem Cells
Retrospective Studies
Regression Analysis
Transplants
Voriconazole

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Analysis of the variable factors influencing tacrolimus blood concentration during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation. / Suetsugu, Kimitaka; Ikesue, Hiroaki; Miyamoto, Toshihiro; Shiratsuchi, Motoaki; Yamamoto-Taguchi, Nanae; Tsuchiya, Yuichi; Matsukawa, Kumi; Uchida, Mayako; Watanabe, Hiroyuki; Akashi, Koichi; Masuda, Satohiro.

In: International Journal of Hematology, Vol. 105, No. 3, 01.03.2017, p. 361-368.

Research output: Contribution to journalArticle

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abstract = "The aim of this retrospective study was to identify variable factors affecting tacrolimus blood concentration during the switch from continuous intravenous infusion to twice-daily oral administration in allogeneic hematopoietic stem cell transplant recipients (n = 73). The blood concentration/dose ratio of tacrolimus immediately before the change from continuous infusion (C/Div) was compared with that between 3 and 5 days after the change to oral administration (C/Dpo). Median (C/Dpo)/(C/Div) was 0.21 (range 0.04–0.58). Multiple regression analysis showed that concomitant use of oral itraconazole or voriconazole significantly increased the (C/Dpo)/(C/Div) of tacrolimus (p = 0.002), probably owing to the inhibition of enterohepatic cytochrome P450 3A4. In addition, 5 of 18 (28{\%}) patients who had the lowest quartile (C/Dpo)/(C/Div) values developed acute graft-versus-host-disease (GVHD), which was significantly higher than in others [5 of 55 (9{\%}) patients, p = 0.045]. Although the switch from intravenous to oral administration at a ratio of 1:5 appeared to be appropriate, a lower conversion ratio was suitable in patients taking oral itraconazole or voriconazole. In patients whose blood concentration decreases after the switch, the development of GVHD should be monitored and tacrolimus dosage should be readjusted to maintain an appropriate blood concentration.",
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