Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient

Satohiro Masuda, Shinji Uemoto, Tohru Hashida, Yukihiro Inomata, Koichi Tanaka, Ken Ichi Inui

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

We have examined whether the expression levels of the intestinal absorptive barriers, MDR1 gene product P-glycoprotein and cytochrome P450 IIIA4 (CYP3A4), correlate with the trough levels of orally administered tacrolimus in a recipient of small bowel transplant for 4 months. By using a competitive polymerase chain reaction, the expression of MDR1 messenger RNA (mRNA) and CYP3A4 mRNA by intestinal cells in a part of the mucosa biopsy specimen was evaluated. The average mRNA expression levels of MDR1 and CYP3A4 were 8.6 and 39.6 amol/μg total RIGA, respectively. Both the MDR1 and CYP3A4 mRNA levels changed markedly throughout this period. The tacrolimus concentration/dose ratio correlated well with the mRNA expression level of MDR1, but not CYP3A4. These results suggested that intestinal P-glycoprotein rather than CYP3A4 is a good probe to predict the intraindividual variation in the tacrolimus pharmacokinetics during immunosuppressant therapy after small bowel transplantation.

Original languageEnglish
Pages (from-to)98-103
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume68
Issue number1
DOIs
Publication statusPublished - Aug 19 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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