Severe elevations of FK506 blood concentration due to diarrhea in renal transplant recipients

Koichiro Sato, Noritoshi Amada, Takaomi Sato, Shunji Miura, Yoichi Ohashi, Satoshi Sekiguchi, Susumu Satomi, Hajime Okazaki

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: The rate of metabolism in the intestine of oral administered FK506 decreases as FK506 passes on to the lower intestine. In transplant recipients with diarrhea given oral FK506, the main areas for absorption of FK506 shift to the lower intestine, where the ability to metabolize FK506 is weaker. Therefore it is considered likely that when FK506 is administered to recipients with diarrhea, the blood concentration of FK506 will be higher. Material and Methods: Twenty recipients experiencing episodes of diarrhea were investigated to determine the trough level of FK506 and the time required for the FK506 trough level to return to the level that obtained before diarrhea. AUC0-4h and Cmax of FK506 were investigated in eight recipients. In cases with severe diarrhea, the daily fluctuations of FK506 blood concentration were also investigated. Result: The FK506 trough level (p < 0.0001), AUC (p = 0.0173), and Cmax (p = 0.0173) were found to be significantly higher during episodes of diarrhea. In almost all cases, it took between 2 and 4 wk for the elevated FK506 trough level to return to its previous level following a bout of diarrhea. In the daily fluctuations of FK506 concentration, Tmax was prolonged. In some cases, the concentration was highest just before administration of FK506, when it should have been at trough level. Conclusions: Diarrhea caused significant elevations of trough level, AUC0-4h and Cmax of FK506, and the prolongation of Tmax in renal transplant recipients administered FK506.

Original languageEnglish
Pages (from-to)585-590
Number of pages6
JournalClinical Transplantation
Volume18
Issue number5
DOIs
Publication statusPublished - 2004 Oct 1

Keywords

  • Area under the concentration-time curve
  • Diarrhea
  • FK506
  • Trough level

ASJC Scopus subject areas

  • Transplantation

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    Sato, K., Amada, N., Sato, T., Miura, S., Ohashi, Y., Sekiguchi, S., Satomi, S., & Okazaki, H. (2004). Severe elevations of FK506 blood concentration due to diarrhea in renal transplant recipients. Clinical Transplantation, 18(5), 585-590. https://doi.org/10.1111/j.1399-0012.2004.00232.x