他克莫司缓释剂治疗儿童原发性肾病综合征的药代动力学特点（英文）

发布时间：2018-02-02 04:55

  本文关键词： 他克莫司 缓释剂 单次口服 儿科 药代动力学　出处：《北京大学学报(医学版)》2017年05期 　论文类型：期刊论文

【摘要】：目的:他克莫司是一种新型钙调磷酸酶抑制剂,目前被广泛应用于成人肝或肾移植术后,也被逐渐广泛应用于肾病综合征患儿。他克莫司缓释胶囊是每日单次口服的缓释剂型,本研究目的是初步探讨他克莫司缓释剂治疗儿童原发性肾病综合征的药代动力学特征。方法:8例受试者系北京大学第一医院2011年6—8月原发性肾病综合征患儿。晨起单次口服不同剂量他克莫司缓释胶囊,给药剂量分别为0.02 mg/kg(n=2)、0.05 mg/kg(n=2)、0.10 mg/kg(n=4),在服药前及服药后1、2、4、6、8、10、12 h分别取静脉血1~2 mL,受试者不用影响他克莫司浓度的其他药物、食物及饮料。采用酶放大免疫分析法,测定他克莫司血药浓度,以Phoenix计算其药代动力学参数。结果:药代动力学数据采用非房室模型分析。3个剂量组(0.02 mg/kg,0.05 mg/kg和0.10 mg/kg)药代动力学参数如下:血药峰浓度分别为(1.7±1.0)μg/L,(3.1±1.9)μg/L,(8.0±3.5)μg/L;药物浓度-时间曲线下面积分别为(47.2±47.1)h·μg/L,(84.0±13.1)h·μg/L,(175.6±107.1)h·μg/L;表观清除率分别为(0.8±0.9)L/(h·kg),(0.4±0.1)L/(h·kg),(1.9±1.3)L/(h·kg);经剂量归一化的表观分布容积分别为(7.0±3.4)L/kg,(12.4±8.4)L/kg,(73.6±68.6)L/kg。0.05 mg/kg剂量组经剂量归一化的血药峰浓度和经剂量归一化的药物浓度-时间曲线下面积的平均值均高于0.02 mg/kg及0.10 mg/kg剂量组。3个剂量组的药物浓度-时间曲线均呈现2次高峰,第一次高峰出现在服药后约2 h,服药后约12 h出现次级高峰;0.10 mg/kg剂量组药物浓度出现两次峰值的现象较0.02 mg/kg及0.05 mg/kg剂量组更显著。结论:他克莫司缓释剂治疗原发性肾病综合征患儿的药代动力学存在个体间差异,本研究初步探讨了他克莫司缓释剂治疗儿童原发性肾病综合征的药代动力学特征,为后续大样本的研究提供了参考依据。
[Abstract]:Objective: tacrolimus is a new type of calmodulin inhibitor, which is widely used after adult liver or kidney transplantation. Tacrolimus sustained-release capsule is a single oral sustained-release drug for children with nephrotic syndrome. The aim of this study was to investigate the pharmacokinetic characteristics of tacrolimus in the treatment of children with primary nephrotic syndrome. Eight subjects were children with primary nephrotic syndrome (PNS) from 2011 to August in Peking University first Hospital. Tacrolimus sustained release capsule with different doses was given orally in the morning. The dosages were 0.02 mg / kg / kg ~ (2) ~ (2) ~ 0. 05 mg / kg / kg ~ (2) ~ (-1) mg / kg ~ (-1) ~ (2) ~ (4) ~ (4), respectively. The venous blood was taken for 12 hours. The subjects did not use other drugs, foods and beverages that affected the concentration of tacrolimus. Enzyme amplification immunoassay was used. The pharmacokinetic parameters of tacrolimus were calculated by Phoenix. Results: the pharmacokinetic data were analyzed by non-atrioventricular model. The pharmacokinetic parameters of 0. 05 mg/kg and 0. 10 mg / kg were as follows: plasma peak concentration was 1. 7 卤1. 0 渭 g 路L ~ (-1) 渭 g / L ~ (-1) 卤1. 9 渭 g 路L ~ (-1) 路L ~ (-1). 8. 0 卤3. 5) 渭 g / L; The area under the concentration-time curve was 47.2 卤47.1 h 路渭 g / L respectively. 175.6 卤107.1 h 路渭 g / L; The apparent clearance rates were 0. 8 卤0. 9 L / L / h 路kg ~ (-1) and 0. 4 卤0. 1 L / 路kg ~ (-1) L / L 路kg ~ (-1) 路kg ~ (-1) 路kg ~ (-1) 路kg ~ (-1); The apparent distribution volumes of the dose normalized were 7.0 卤3.4 L / kg and 12.4 卤8.4 L / kg, respectively. 73.6 卤68.6). The average area under the dose-normalized plasma peak concentration and dose-normalized drug concentration-time curve in the L- (kg 路0.05) mg/kg group was higher than 0. 02. The concentration-time curves of mg/kg and 0.10 mg/kg groups showed two peaks. The first peak appeared at about 2 hours after administration, and the secondary peak appeared at about 12 hours after administration. The drug concentration in the 0. 10 mg/kg group was significantly higher than that in the 0. 02 mg/kg and 0. 05 mg/kg groups. There were individual differences in pharmacokinetics of tacrolimus in the treatment of primary nephrotic syndrome. The pharmacokinetics of tacrolimus in the treatment of children with primary nephrotic syndrome was studied in this study.
【作者单位】： 北京大学第一医院儿科;北京大学第一医院药剂科;武汉市儿童医院肾内科;
【分类号】：R726.9
【正文快照】： 内科,武汉430015)△Corresponding author’s e-mail,huijiexiao2@hotmail.com,zhouying0321@126.com网络出版时间:2017-9-4 16:17:32网络出版地址:http://www.cnki.net/kcms/detail/11.4691.R.20170904.1617.020.html(n=2)、0.10 mg/kg(n=4),在服药前及服药后1、2、4、6、8、，

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