Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient |
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Authors: | Masuda S Uemoto S Hashida T Inomata Y Tanaka K Inui K |
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Affiliation: | Department of Pharmacy, Kyoto University Hospital, Japan. |
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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/microg total RNA, 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. |
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