[Purpose]To prevent acute rejection for renal transplantation, a combination immunosuppressive therapy of calucineurin inhibitors, antimetabolites, and steroids is usually provided. In the immunosuppressive therapy which uses high-dose mizoribine (MZ: 6 mg/ kg/ day) for antimetabolites, referred to as high-dose MZ therapy, it has been a problem that the individual difference of the blood concentration of MZ is large. MZ is a renal excretion drug, but the change between the individual of the absorption factor is remarkable, and the absorption of MZ becomes the factor which has an influence on the blood concentration following renal function. However, long-term changes in MZ absorption in individual patients have not been studied. We thus evaluated intra-individual MZ absorption changes.[Methods]Our study included patients receiving high-dose MZ therapy after living renal transplantations, performed between March 2007 and December 2014, and whose blood MZ data at 2 weeks, 4 weeks and 1 year postoperatively were available. We evaluated changes in “apparent absorption” defined as the area under the blood concentration-time curve corrected with renal function and dose (AUC・eGFR/ Dose) of MZ in each patient. We also evaluated how patient demographics (age, male/female ratio, concomitant CNI, whether the patient had been on dialysis before the operation, preoperative dialysis duration, preoperative glucose metabolism) affected the changes in “apparent absorption”.[Results]“Apparent absorption” was significantly increased at 4 weeks after renal transplantation, as compared with 2 weeks thereafter (mean rate of change, 130%) and was significantly decreased at 1 year as compared with 4 weeks after receiving a donor kidney (mean rate of change, 85%). Patient demographics did not affect “apparent absorption”. [Discussion]Our study showed the duration of MZ treatment to affect absorption changes with high-dose MZ therapy. Then this result, it was confirmed that enforcement of therapeutic drug monitoring was important to give high-dose MZ therapy appropriately. Moreover, we propose that when planning to administer MZ, we should take particular note of the duration of MZ treatment.
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