Naito Takafumi, Mino Yasuaki, Otsuka Atsushi, Ushiyama Tomomi, Ozono Seiichiro, Kagawa Yoshiyuki, Kawakami Junichi
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Biol Pharm Bull. 2008 Jun;31(6):1292-6. doi: 10.1248/bpb.31.1292.
The aim of this study was to evaluate the plasma trough concentrations (C(0)) of mycophenolic acid (MPA) and its major metabolite MPA 7-O-glucuronide (MPAG) in metal cation (MC)(-) (non-treated) and MC(+) (co-treated) patients who received tacrolimus (Tac) or cyclosporine (CyA). Fifty-nine Japanese stable kidney transplant recipients receiving immunosuppressive regimens containing mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI) were included in this study. Seven in the 25 patients receiving Tac and 8 in the 34 patients receiving CyA were treated with concomitant MCs administration. Multiple regression analysis revealed that concomitant MCs and CyA administration influenced MPA C(0). Their standardized partial regression coefficients were -0.29 and -0.41, respectively. Stratified analysis based on CNI treatment revealed that MPA C(0) decreased significantly by 56% with concomitant MCs administration in Tac-treated patients. There was no significant difference in MPA C(0) between the MC(-) and MC(+) groups in CyA-treated patients. With respect to MPAG C(0), MC(+) group tended to be lower by 26% than MC(-) group in Tac-treated patients. There was no significant difference in MPAG C(0) between the MC(-) and MC(+) groups in CyA-treated patients. Concomitant MCs administration did not affect the C(0) ratio of MPAG to MPA in either Tac- or CyA-treated patients. In conclusion, MCs co-administration decrease MPA C(0) in patients receiving Tac and may cause lower MPA exposure. There are little pharmacokinetic interactions between MMF and concomitant MCs in CyA-treated patients.
本研究旨在评估接受他克莫司（Tac）或环孢素（CyA）治疗的金属阳离子（MC）（-）（未治疗）和MC（+）（联合治疗）患者中霉酚酸（MPA）及其主要代谢产物MPA 7 - O - 葡萄糖醛酸苷（MPAG）的血浆谷浓度（C(0)）。59名接受含霉酚酸酯（MMF）和钙调神经磷酸酶抑制剂（CNI）免疫抑制方案的日本稳定肾移植受者纳入本研究。接受Tac治疗的25名患者中有7名和接受CyA治疗的34名患者中有8名接受了MC联合给药。多元回归分析显示，MC与CyA联合给药会影响MPA的C(0)。它们的标准化偏回归系数分别为-0.29和-0.41。基于CNI治疗的分层分析显示，在接受Tac治疗的患者中，MC联合给药使MPA的C(0)显著降低了56%。在接受CyA治疗的患者中，MC（-）组和MC（+）组之间的MPA C(0)没有显著差异。关于MPAG的C(0)，在接受Tac治疗的患者中，MC（+）组比MC（-）组低26%。在接受CyA治疗的患者中，MC（-）组和MC（+）组之间的MPAG C(0)没有显著差异。在接受Tac或CyA治疗的患者中，MC联合给药均不影响MPAG与MPA的C(0)比值。总之，MC联合给药会降低接受Tac治疗患者的MPA C(0)，可能导致MPA暴露量降低。在接受CyA治疗的患者中，MMF与MC联合给药之间几乎没有药代动力学相互作用。
