About the influence which aging has on absorption of mizoribine -In the high-dose mizoribine combination immunosuppressive therapy for renal transplantation-

DOI
  • Ohigashi Mariko
    Department of Pharmacy, University Hospital, Kyoto Prefectural University of Medicine
  • Koshino Katsuhiro
    Department of Organ Transplant and General Surgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences
  • Nakagawa Tomoka
    Department of Organ Transplant and General Surgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences
  • Kosaka Tadashi
    Department of Pharmacy, University Hospital, Kyoto Prefectural University of Medicine
  • Ushigome Hidetaka
    Department of Organ Transplant and General Surgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences
  • Yoshimura Norio
    Department of Organ Transplant and General Surgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences
  • Shikata Keisuke
    Department of Pharmacy, University Hospital, Kyoto Prefectural University of Medicine

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Other Title
  • ミゾリビンの吸収に加齢が及ぼす影響について─腎移植後の高用量ミゾリビン併用免疫抑制療法において─

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<p>[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. Therefore, we examined the influence which aging has on absorption of mizoribine.[Methods]　The target population of our research was 50 patients who had received high-dose MZ therapy from April 2011 to September 2013. We divided the patients into two groups: the low age group (18-44 years: 25 patients), and the older age group (45 years and older: 25 patients).In two groups, we performed the comparison analysis of the blood concentration of MZ and the pharmacokinetic parameter. In addition, we examined the correlation between age and values of the area under the blood concentration time curve corrected for creatinine clearance and dose (AUC･Ccr/ Dose).[Results]　The significant difference of the transplant renal function was not seen between two age groups. In the low age group, the trough level and AUC were significantly higher than that in the older age group. We also found a negative correlation between age and the AUC･Ccr/ Dose.[Discussion]　It was supposed a drop of the absorption of MZ by the aging. Than 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 age.</p>

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