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.
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.
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.|Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kimitaka
K
Suetsugu
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Hiroaki
H
Ikesue
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Toshihiro
T
Miyamoto
Department of Medicine and Bioregulatory Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Motoaki
M
Shiratsuchi
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Nanae
N
Yamamoto-Taguchi
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Yuichi
Y
Tsuchiya
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Kumi
K
Matsukawa
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Mayako
M
Uchida
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Hiroyuki
H
Watanabe
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Koichi
K
Akashi
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. satomsdb@pharm.med.kyushu-u.ac.jp.|Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. satomsdb@pharm.med.kyushu-u.ac.jp.
Satohiro
http://orcid.org/0000-0002-3589-5989
S
Masuda
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D064591:Allografts; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D017964:Itraconazole / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood; D065819:Voriconazole / Q000627:therapeutic use
D017964:Itraconazole; D065819:Voriconazole; D016559:Tacrolimus
Blood concentration; Hematopoietic stem cell transplantation; Route switch; Tacrolimus