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 language | English |
|---|---|
| Pages (from-to) | 1728-1729 |
| Number of pages | 2 |
| Journal | Transplantation Proceedings |
| Volume | 37 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - May 1 2005 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Initial dosage adjustment for oral administration of tacrolimus using the intestinal MDR1 level in living-donor liver transplant recipients
AU - Masuda, Satohiro
AU - Goto, M.
AU - Okuda, M.
AU - Ogura, Y.
AU - Oike, F.
AU - Kiuchi, T.
AU - Tanaka, K.
AU - Inui, K.
PY - 2005/5/1
Y1 - 2005/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20344379217&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20344379217&partnerID=8YFLogxK
U2 - 10.1016/j.transproceed.2005.02.081
DO - 10.1016/j.transproceed.2005.02.081
M3 - Article
C2 - 15919446
AN - SCOPUS:20344379217
VL - 37
SP - 1728
EP - 1729
JO - Transplantation Proceedings
JF - Transplantation Proceedings
SN - 0041-1345
IS - 4
ER -