In a prospective study, Thervet et al. divided MK-8669 kidney transplantation patients into groups that did and did not have the initial Tac dose set based on CYP3A5 polymorphism and studied the subsequent pharmacokinetics.[20] The percentage of patients achieving the optimal trough level after six oral administrations, which was the primary end-point, was significantly higher in the group with the initial Tac dose set based on CYP3A5 polymorphism than in the group with the dose not set based on CYP3A5 polymorphism (43.2% vs 29.1%). There have been no such studies in the field of IBD; this is the first such report. In the present study,

the trough and dose-adjusted trough levels were significantly higher on days 2–5 and 7–10 in the CYP3A5 Non-Exp group than in the CYP3A5 Exp group. Moreover, on both days 2–5 and 7–10, the percentage of patients achieving the optimal trough level was significantly higher in the Non-Exp group than in the Exp group. Higher trough levels were also

obtained with low Tac doses in the Non-Exp group than in the Exp group among UC patients, and the optimal trough level was shown to be achieved at an early time. In an analysis of factors involved in achieving the optimal trough level on days 2–5, CYP3A5 genetic polymorphisms and food intake/non-intake were significant factors on multivariate analysis. Only CYP3A5 genetic polymorphisms were significant on days 7–10. Although the effects of both CYP3A5 and fasting became weak with time, CYP3A5

mTOR inhibitor polymorphism was the only significant factor because of its strong impact. Thus, the results showed that consideration of CYP3A5 genetic polymorphisms is important for early induction of the optimal trough level. ABCB1 is also reported to be associated with Tac pharmacokinetics, although its effect is smaller than that of CYP3A5 genetic polymorphisms.[21] However, involvement of ABCB1 and MCE CYP3A4 genetic polymorphisms in the trough level was not seen in the present study. Clinical remission was evaluated 4 weeks after the start of therapy in the present study using the pDAI score, which excluded the endoscopy score. The partial Mayo score has also been used to determine clinical efficacy in recent large-scale studies.[22, 23] Judging clinical efficacy with an activity index that excludes the endoscopy score is thought to have a certain level of validity.[24] Because the Mayo score and DAI are essentially the same score, in this study, DAI, which can be determined in a single day, was adopted.[25] The remission rate was significantly higher in the Non-Exp group than in the Exp group. All four patients who underwent surgery within 4 weeks after the start of therapy were in the Exp group. These results are interpreted as showing a higher likelihood of achieving the optimal trough level, resulting in a tendency for a better therapeutic response, in the Non-Exp group. Herrlinger et al.