Masuda S, Uemoto S, Hashida T, Inomata Y, Tanaka K, Inui K
Department of Pharmacy, Kyoto University Hospital, Japan.
Clin Pharmacol Ther. 2000 Jul;68(1):98-103. doi: 10.1067/mcp.2000.107912.
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.
我们研究了小肠移植受者肠道吸收屏障、多药耐药基因1（MDR1）产物P-糖蛋白和细胞色素P450 IIIA4（CYP3A4）的表达水平与口服他克莫司谷浓度之间是否相关，该研究持续了4个月。通过竞争性聚合酶链反应，评估了部分黏膜活检标本中肠细胞的MDR1信使核糖核酸（mRNA）和CYP3A4 mRNA的表达。MDR1和CYP3A4的平均mRNA表达水平分别为8.6和39.6 amol/μg总RNA。在此期间，MDR1和CYP3A4的mRNA水平均发生了显著变化。他克莫司浓度/剂量比值与MDR1的mRNA表达水平密切相关，但与CYP3A4无关。这些结果表明，肠道P-糖蛋白而非CYP3A4是预测小肠移植后免疫抑制治疗期间他克莫司药代动力学个体内差异的良好指标。
