Required transient dose escalation of tacrolimus in living-donor liver transplant recipients with high concentrations of a minor metabolite M-II in bile

Masahiro Shimomura, Satohiro Masuda, Maki Goto, Toshiya Katsura, Tetsuya Kiuchi, Yasuhiro Ogura, Fumitaka Oike, Yasutsugu Takada, Shinji Uemoto, Ken Ichi Inui

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The profiles of tacrolimus metabolites in the whole blood and bile were examined in two living-donor liver transplant patients, who transiently required higher doses of tacrolimus. Even when the 16 mg/day or oral 10 mg/day and intravenous infusion of 0.5 mg/day of tacrolimus were administered, its trough level in each patient did not reach over 15 ng/ mL. By use of liquid chromatography-tandem mass spectrometry/mass spectrometry methods, a minor metabolite M-II was found to be a major metabolite both in blood and bile in these cases. However, a primary metabolite M-I was confirmed as the majority in the bile of other 8 control cases. Each graft liver and native intestine carried CYP3A5*1/*3 or *3/*3 and *1/*3 or *1/*3, respectively. Therefore, the CYP3A5 genotype could not explain the present phenomena. After removing the bile drainage tube to allow the bile flow into intestine, the required doses of tacrolimus were decreased to around 20% compared to each maximum dosage. In conclusion, a minor metabolite M-II was first found in the human bile, suggesting that the appearance of M-II in bile could associate with the extensive metabolism of tacrolimus and/or the requirement of larger oral dosage.

Original languageEnglish
Pages (from-to)313-317
Number of pages5
JournalDrug metabolism and pharmacokinetics
Volume23
Issue number5
DOIs
Publication statusPublished - Jan 1 2008

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Required transient dose escalation of tacrolimus in living-donor liver transplant recipients with high concentrations of a minor metabolite M-II in bile'. Together they form a unique fingerprint.

  • Cite this

    Shimomura, M., Masuda, S., Goto, M., Katsura, T., Kiuchi, T., Ogura, Y., Oike, F., Takada, Y., Uemoto, S., & Inui, K. I. (2008). Required transient dose escalation of tacrolimus in living-donor liver transplant recipients with high concentrations of a minor metabolite M-II in bile. Drug metabolism and pharmacokinetics, 23(5), 313-317. https://doi.org/10.2133/dmpk.23.313