Initial dosage adjustment for oral administration of tacrolimus using the intestinal MDR1 level in living-donor liver transplant recipients

Satohiro Masuda, M. Goto, M. Okuda, Y. Ogura, F. Oike, T. Kiuchi, K. Tanaka, K. Inui

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The role of intestinal P-glycoprotein (encoded by the MDR1/ABCB1 gene) and/or metabolic enzyme CYP3A4 for tacrolimus therapy was examined in recipients of living-donor liver transplantation (LDLT), under the hypothesis that these proteins are factors for pharmacokinetic variability. The intestinal mRNA expression level of MDR1 and CYP3A4 was evaluated by real-time polymerase chain reaction (PCR), using the upper jejunum from a part of the Roux-en-Y limb for biliary reconstruction at LDLT. For 7 days postoperatively, good inverse correlation was found between the tacrolimus concentration/dose (C/D) ratio and the intestinal mRNA level of MDR1 (r = -0.776), but not of CYP3A4 (r = -0.096), in the 46 cases. After classifying the patients according to median of the intestinal MDR1 mRNA expression, the oral dose of tacrolimus in the high-MDR1 group was approximately twofold higher than in the low-MDR1 group (P <. 001), whereas its trough level was similar between the two groups. In addition, the correlation between the intestinal MDR1 mRNA level and the tacrolimus C/D ratio was confirmed with a larger population (r = -0.645, n = 104). Using the regression line between the intestinal MDR1 mRNA level and tacrolimus C/D ratio, we could prospectively predict the individual C/D ratio of tacrolimus immediately after LDLT. Known genetic variations of the MDR1 gene had no effect on intestinal MDR1 mRNA level and tacrolimus C/D ratio in LDLT patients. This suggests that the intestinal mRNA level of MDR1 is a useful molecular marker for determination of the personalized oral dose of tacrolimus in recipients of LDLT immediately after surgery.

Original languageEnglish
Pages (from-to)1728-1729
Number of pages2
JournalTransplantation Proceedings
Volume37
Issue number4
DOIs
Publication statusPublished - May 1 2005
Externally publishedYes

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Living Donors
Tacrolimus
Oral Administration
Liver Transplantation
Liver
Messenger RNA
Cytochrome P-450 CYP3A
Transplant Recipients
P-Glycoprotein
Jejunum
Genes
Real-Time Polymerase Chain Reaction
Extremities
Pharmacokinetics
Enzymes
Population

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

Initial dosage adjustment for oral administration of tacrolimus using the intestinal MDR1 level in living-donor liver transplant recipients. / Masuda, Satohiro; Goto, M.; Okuda, M.; Ogura, Y.; Oike, F.; Kiuchi, T.; Tanaka, K.; Inui, K.

In: Transplantation Proceedings, Vol. 37, No. 4, 01.05.2005, p. 1728-1729.

Research output: Contribution to journalArticle

Masuda, Satohiro ; Goto, M. ; Okuda, M. ; Ogura, Y. ; Oike, F. ; Kiuchi, T. ; Tanaka, K. ; Inui, K. / Initial dosage adjustment for oral administration of tacrolimus using the intestinal MDR1 level in living-donor liver transplant recipients. In: Transplantation Proceedings. 2005 ; Vol. 37, No. 4. pp. 1728-1729.
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