Tacrolimus (FK506) - Its effects on intestinal glucose transport

Natalie L. Yanchar, Timothy M. Riegel, Gary Martin, Richard N. Fedorak, Norman M. Kneteman, David L. Sigalet

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Tacrolimus (FK506) is at present the mainstay of immunosuppression for small intestinal transplantation. This study investigates the effects of chronic treatment with varying dosages of tacrolimus on animal well-being, weight gain, intestinal permeability, and the active transport of nutrients as measured by in vitro studies quantifying glucose flux. The effect of acute treatment with high-dose tacrolimus on glucose flux was also investigated. In the chronic studies, juvenile male Lewis rats were given tacrolimus in a dosage of 0.1 mg/kg, 0.5 mg/kg, and 2 mg/kg q. second day by subcutaneous injection for five weeks. In the acute studies, animals were treated with 2 mg/kg given q. 24 hr [multi 48 hr, 24 hr and 12 hr prior to sacrifice. In the acute treatment groups, tacrolimus caused no change in glucose flux. In the chronically treated animals, FK506 levels were within the clinically relevant range. Chronic treatment with 0.5 and 2 mg/kg caused a significant reduction in weight gain. These same groups of animals had a significant increase in intestinal permeability as measured by absorption of 99Te-DTPA. Glucose flux was affected in all chronically treatment groups, with net flux increasing in the jejunum and decreasing in the ileum. These findings show that chronic treatment with low-dose tacrolimus is well tolerated, but in higher doses there are significant effects in intestinal permeability and nutrient uptake, and animal weight gain. We suggest that these changes are due to alterations in intestinal permeability that do not appear to mediated by an acute drug effect and more likely represent chronic changes, possibly from alterations in gene expression. These findings suggest that further studies regarding the effects of tacrolimus on nutrient transport, intestinal permeability, and the known immunologically related functions of tacrolimus should be done.

Original languageEnglish
Pages (from-to)630-634
Number of pages5
JournalTransplantation
Volume61
Issue number4
DOIs
Publication statusPublished - Feb 27 1996
Externally publishedYes

ASJC Scopus Subject Areas

  • Transplantation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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