[12] In that study, the therapeutic effect was determined 6 weeks after the start of Tac, and it was effective in 75% of cases (61% remission and 14% improvement). It was found that CYP3A4 and CYP3A5 genetic polymorphisms were not associated with efficacy and that the presence or absence of TT type in the 1236C/T, 2677G/T/A, and 3435C/T of ABCB1 was related to the clinical effect. Several differences are thought to be causative factors in this difference from the present study. One major difference is the PD0332991 cell line racial difference

in genetic polymorphisms of CYP3A4, CYP3A5, and ABCB1.[9-11] There is a large difference in CYP3A5 Non-Exp in particular at 35–65% in Asians and 85–90% in Caucasians.[9-11] In fact, CYP3A5 Non-Exp accounted for 89.9% in the report by Herrlinger et al.,[12] clearly higher than the 46.7% in the present study. Nearly 90% of patients were Non-Exp, and

this is thought to be why CYP3A5 genetic polymorphisms did not affect the Midostaurin concentration percentage of patients achieving the optimal trough level and the clinical effect. It may be inferred that the high remission rate of 61% is attributable to the fact that the subjects were Caucasians, a population susceptible to the effects of Tac. As for adverse effects, the results of the current study were similar to other reports.[3, 26] There were no differences in the frequencies of adverse effects between the Exp group and the Non-Exp group. A limitation of this study is that the analysis was done with a small number

of UC patients in a single institution. However, the results of genetic polymorphisms of CYP3A4, CYP3A5, and ABCB1 were nearly the same as in previously reported analyses of Asian patients.[14, 17] The pharmacokinetics and therapeutic effect of Tac were investigated in IBD patients, and interesting new findings were obtained, namely that CYP3A5 Non-Exp is associated with achieving the optimal Tac trough level and short-term clinical remission. These findings suggest that understanding the genetic polymorphisms of CYP3A5 in UC check details patients is useful in controlling the dosage, such as establishing higher initial dosages in Exp than in Non-Exp and establishing greater increases when changing the dose after confirming the trough level. Thus, it may be possible to implement tailor-made medicine suited to the individual case in the therapy of UC patients. Interestingly, there is some doubt as to a relationship between the pharmacokinetics of cyclosporine, also a calcineurin inhibitor, and CYP3A5 genetic polymorphisms.[27-30] Cyclosporine is also used in treating UC, but unlike Tac, no advantages can be expected from confirming the CYP3A5 genetic polymorphisms. In conclusion, this study showed that CYP3A5 genetic polymorphisms affect the pharmacokinetics of Tac and short-term clinical remission, at least in Asian patients. Various factors are thought to be related to the individual differences in Tac treatment effect.