Order-made pharmacotherapy based on MDR1 genotyping

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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.