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  • Title: Tacrolimus therapy according to mucosal MDR1 levels in small-bowel transplant recipients.
    Author: Masuda S, Uemoto S, Goto M, Fujimoto Y, Tanaka K, Inui K.
    Journal: Clin Pharmacol Ther; 2004 Apr; 75(4):352-61. PubMed ID: 15060513.
    Abstract:
    To clarify the clinical applicability of intestinal absorptive barriers, we have quantified messenger ribonucleic acid (mRNA) expression levels of multidrug resistance 1 (MDR1) protein and cytochrome P450 (CYP) 3A4 in intestinal biopsy specimens from 2 small-bowel transplant recipients. Postoperative immunosuppressive therapy was started with intravenous and oral administrations of tacrolimus and a small amount of steroids. The daily dosage of tacrolimus was modified mainly on the basis of trough levels. After confirmation that the enterocyte MDR1 level was decreasing, tacrolimus was administered via the oral route only. The mRNA levels in the biopsy specimens varied widely throughout the period. With high-dose steroid-pulse treatment, the enterocyte mRNA expression of CYP3A4, but not of MDR1, was markedly enhanced. The mRNA levels of MDR1, but not CYP3A4, correlated well with the concentration/oral dose ratio and the oral dosage of tacrolimus. The good progress after transplantation in both cases suggested that monitoring the change in expression of MDR1 mRNA in the graft intestine might be helpful for understanding the pharmacokinetic profile and determining when to change the route of tacrolimus administration in small-bowel transplant recipients.
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