Order-made pharmacotherapy based on MDR1 genotyping

本研究旨在探讨MDR1基因分型建立处方药物治疗的可能性。MDR1是一种170kDa的膜蛋白，在肠、脑、肾等正常组织中均有表达，是外源性毒性物质向细胞外的外排转运体，调节多种药物的药代动力学。在此，我们阐明了1)地高辛单次口服后的血清浓度-时间谱由位于外显子26的MDR1 C3435T决定；2) MDR1 mRNA在肠黏膜中的表达也通过MDR1 C3435T来确定。简而言之，携带c等位基因的受试者地高辛浓度较高，MDR1 mRNA表达较低。通过对健康受试者的调查，我们还发现环孢素的药代动力学符合MDR1 C3435T。这些数据发表为6篇原创文章和4篇综述文章。

This research was conducted to examine the possibility of MDR1 genotyping to establish the order-made pharmacotherapy. MDR1 is a 170kDa membrane protein, which is expressed in the normal tissues including intestine, brain and kidneys, and acts as efflux transporter of exogenous toxic substances out of the cells, and therefore regulates the pharmacokinetics of a number of drugs. Herein, we elucidated that 1)the serum concentration-time profiles of digoxin after single oral administration was defined by MDR1 C3435T, located in exon 26; 2)the expression of MDR1 mRNA in the intestinal mucosa was defined also by MDR1 C3435T. Briefly, the digoxin concentrations were higher in the subjects with C-allele, and the expression of MDR1 mRNA was lower in the subjects. Based on these investigations with healthy subjects, we also found that 3)cyclosporine pharmacokinetics was defined by MDR1 C3435T. These data were published as 6 original articles and 4 review articles.