Population pharmacokinetics of mizoribine in pediatric patients with kidney disease
Population pharmacokinetics of mizoribine in pediatric patients with kidney disease
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DOI：
10.1007/s10157-015-1209-9
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发表时间：
2016-10-01
影响因子：
2.3
通讯作者：
Uemura, Osamu
中科院分区：
文献类型：
--
作者：
Kaneda, Hisashi;Shimizu, Masaki;Uemura, Osamu
本研究旨在获得优化咪唑立宾（MZR）治疗儿童肾脏病的临床效果的信息，共纳入105例在我院治疗的儿童肾脏病患者。肾移植患者被排除在外。根据血药浓度数据进行MZR群体药代动力学分析。通过Bayesian分析计算从时间0到无穷大的曲线下面积（AUC（a））和最大浓度（C（max））。与健康成人相比，儿童中MZR在血液中的出现倾向于较慢，随后的血药浓度上升倾向于更缓慢。儿童的表观分布容积和口服清除率也高于成人。观察到患者年龄与AUC（a）之间存在显著正相关。AUC（a）和C（max）在不同年龄组间差异有统计学意义。MZR的给药方法与血药浓度无相关性，儿童与成人的药代动力学不同。为了获得预期的临床疗效，常规MZR给药方案（2-3 mg/kg/天）可能不足以治疗儿科患者。特别是，年轻患者可能需要每单位体重更高剂量的MZR。
The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC(a)) and maximal concentration (C (max)) were calculated by Bayesian analysis.In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC(a). There were significant differences of AUC(a) and C (max) by age group. No relationship was observed between the administration method of MZR and serum concentration.The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2-3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.