The true distribution volume and bioavailability of mizoribine in children with chronic kidney disease
The true distribution volume and bioavailability of mizoribine in children with chronic kidney disease
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DOI：
10.1007/s10157-016-1353-x
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发表时间：
2017-10-01
影响因子：
2.3
通讯作者：
Hashimoto, Yukiya
中科院分区：
文献类型：
--
作者：
Nagai, Takuhito;Uemura, Osamu;Hashimoto, Yukiya
咪唑立宾（MZR）用于肾移植和各种肾脏疾病。然而，很少有研究报道药代动力学和药效学之间的关联。儿科肾病药代动力学研究小组（PSPKD）使用群体药代动力学（PPK）分析和贝叶斯分析来研究MZR的有效性。在这项研究中，几乎所有的MZR都以原型经尿液排泄，这一事实被用来计算其生物利用度（F）和真实分布容积（V（d）），并分析了这些与年龄的相关性。Ishida et al.报告了PSPKD的PPK分析。在本研究中，对从105名年龄在1至20岁之间的儿童慢性肾病患者的研究人群中提取的71个样本进行了研究。通过测量24小时尿样中的总排泄MZR计算生物利用度，并将其与口服剂量进行比较。用Bayesian法计算表观分布容积（V（d）/F），计算真实分布容积（V（d）），并分析各参数与年龄的相关性，MZR中位剂量为5.17 mg/kg/d。中位生物利用度为32.02%。中位V（d）/体重为0.46 L/kg。生物利用度与年龄之间存在显著的弱正相关性（p = 0.026）。V（d）/体重与年龄呈显著的弱负相关（p = 0.003），生物利用度和V（d）/体重随年龄的增加而降低。年轻患者需要更大的剂量来获得MZR的最大效果，这对免疫抑制治疗很重要。
Mizoribine (MZR) is used kidney transplant and various kidney diseases. However, few studies reported the association between pharmacokinetics and pharmacodynamics. The Pharmacokinetics Study Group for Pediatric Kidney Disease (PSPKD) used population pharmacokinetics (PPK) analysis and Bayesian analysis to investigate the usefulness of MZR. In this study, the fact that almost all MZR are excreted unchanged in urine was used to calculate its bioavailability (F) and true distribution volume (V (d)), and analyzed these correlation with age.Ishida et al. reported a PPK analysis by the PSPKD. In the present study, 71 samples extracted from their study population of 105 pediatric chronic kidney disease patients aged between 1 and 20 years were investigated. The bioavailability was calculated by measuring total excreted MZR in 24 h urine samples, and this was compared to the oral dosage. The apparent distribution volume (V (d)/F) obtained from Bayesian analysis was then used to calculate true distribution volume (V (d)), and the correlation of each parameter with age was investigated.The median dose of MZR per weight was 5.17 mg/kg/day. Median bioavailability was 32.02%. Median V (d) per weight was 0.46 L/kg. There was a significant, weakly positive correlation between bioavailability and age (p = 0.026). There was also a significant, weakly negative correlation between V (d) per weight and age (p = 0.003).Bioavailability and V (d) per weight tended to decrease depending on age. The younger patient required larger dose required to obtain the maximum effect from MZR, and this is important for immunosuppressive therapy.