Association between CYP3A5 genotypes in graft liver and increase in tacrolimus biotransformation from steroid treatment in living-donor liver transplant patients

Keiko Hosohata, Miwa Uesugi, Sachiyo Hashi, Mio Hosokawa, Ken Ichi Inui, Kazuo Matsubara, Kohei Ogawa, Yasuhiro Fujimoto, Toshimi Kaido, Shinji Uemoto, Satohiro Masuda

研究成果: Contribution to journalArticle査読

12 被引用数 (Scopus)

抄録

We retrospectively examined whether cytochrome P450 (CYP) 3A5 genotypes are associated with high-dose steroid pulse treatment-induced functional gain of tacrolimus biotransformation in livingdonor liver transplant patients. Concentrations of tacrolimus and its 3 primary metabolites, 13-O-demethyl tacrolimus (M-I), 31-O-demethyl tacrolimus (M-II), and 15-O-demethyl tacrolimus (M-III), were measured in trough blood samples from 18 liver transplant patients, by liquid chromatographytandem mass spectrometry/mass spectrometry (LC-MS/MS). In patients engrafted with a CYP3A5*1-carrying liver but not with a CYP3A5*3/*3-carrying liver, the concentration/dose ratio of tacrolimus significantly fell after therapy, while ratios of M-I/tacrolimus, M-II/tacrolimus, and M-III/tacrolimus were significantly higher after therapy than before (p = 0.032, p = 0.023, and p = 0.0078, respectively). After steroid pulse therapy, the concentration of tacrolimus measured by immunoassay was significantly higher than that measured by LCMS/MS in patients engrafted with a CYP3A5*1-carrying liver, but not those engrafted with a CYP3A5*3/*3-carrying liver. This suggests that the increased ratio of tacrolimus metabolites/tacrolimus can be explained by induction of CYP3A5 via high-dose steroid pulse therapy. Further, the concentrations of tacrolimus measured by the immunoassays were overestimated, partly because of cross-reactivity of the monoclonal antibody they incorporated to detect tacrolimus, with the increased metabolites in patients with a CYP3A5*1-carrying graft liver.

本文言語英語
ページ(範囲)83-89
ページ数7
ジャーナルDrug metabolism and pharmacokinetics
29
1
DOI
出版ステータス出版済み - 2014

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

フィンガープリント 「Association between CYP3A5 genotypes in graft liver and increase in tacrolimus biotransformation from steroid treatment in living-donor liver transplant patients」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル