本文關(guān)鍵詞： 他克莫司 緩釋劑 單次口服 兒科 藥代動力學(xué)　出處：《北京大學(xué)學(xué)報(醫(yī)學(xué)版)》2017年05期 　論文類型：期刊論文

【摘要】：目的:他克莫司是一種新型鈣調(diào)磷酸酶抑制劑,目前被廣泛應(yīng)用于成人肝或腎移植術(shù)后,也被逐漸廣泛應(yīng)用于腎病綜合征患兒。他克莫司緩釋膠囊是每日單次口服的緩釋劑型,本研究目的是初步探討他克莫司緩釋劑治療兒童原發(fā)性腎病綜合征的藥代動力學(xué)特征。方法:8例受試者系北京大學(xué)第一醫(yī)院2011年6—8月原發(fā)性腎病綜合征患兒。晨起單次口服不同劑量他克莫司緩釋膠囊,給藥劑量分別為0.02 mg/kg(n=2)、0.05 mg/kg(n=2)、0.10 mg/kg(n=4),在服藥前及服藥后1、2、4、6、8、10、12 h分別取靜脈血1~2 mL,受試者不用影響他克莫司濃度的其他藥物、食物及飲料。采用酶放大免疫分析法,測定他克莫司血藥濃度,以Phoenix計算其藥代動力學(xué)參數(shù)。結(jié)果:藥代動力學(xué)數(shù)據(jù)采用非房室模型分析。3個劑量組(0.02 mg/kg,0.05 mg/kg和0.10 mg/kg)藥代動力學(xué)參數(shù)如下:血藥峰濃度分別為(1.7±1.0)μg/L,(3.1±1.9)μg/L,(8.0±3.5)μg/L;藥物濃度-時間曲線下面積分別為(47.2±47.1)h·μg/L,(84.0±13.1)h·μg/L,(175.6±107.1)h·μg/L;表觀清除率分別為(0.8±0.9)L/(h·kg),(0.4±0.1)L/(h·kg),(1.9±1.3)L/(h·kg);經(jīng)劑量歸一化的表觀分布容積分別為(7.0±3.4)L/kg,(12.4±8.4)L/kg,(73.6±68.6)L/kg。0.05 mg/kg劑量組經(jīng)劑量歸一化的血藥峰濃度和經(jīng)劑量歸一化的藥物濃度-時間曲線下面積的平均值均高于0.02 mg/kg及0.10 mg/kg劑量組。3個劑量組的藥物濃度-時間曲線均呈現(xiàn)2次高峰,第一次高峰出現(xiàn)在服藥后約2 h,服藥后約12 h出現(xiàn)次級高峰;0.10 mg/kg劑量組藥物濃度出現(xiàn)兩次峰值的現(xiàn)象較0.02 mg/kg及0.05 mg/kg劑量組更顯著。結(jié)論:他克莫司緩釋劑治療原發(fā)性腎病綜合征患兒的藥代動力學(xué)存在個體間差異,本研究初步探討了他克莫司緩釋劑治療兒童原發(fā)性腎病綜合征的藥代動力學(xué)特征,為后續(xù)大樣本的研究提供了參考依據(jù)。
[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 鹵1. 0 渭 g 路L ~ (-1) 渭 g / L ~ (-1) 鹵1. 9 渭 g 路L ~ (-1) 路L ~ (-1). 8. 0 鹵3. 5) 渭 g / L; The area under the concentration-time curve was 47.2 鹵47.1 h 路渭 g / L respectively. 175.6 鹵107.1 h 路渭 g / L; The apparent clearance rates were 0. 8 鹵0. 9 L / L / h 路kg ~ (-1) and 0. 4 鹵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 鹵3.4 L / kg and 12.4 鹵8.4 L / kg, respectively. 73.6 鹵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.
【作者單位】： 北京大學(xué)第一醫(yī)院兒科;北京大學(xué)第一醫(yī)院藥劑科;武漢市兒童醫(yī)院腎內(nèi)科;
【分類號】：R726.9
【正文快照】： 內(nèi)科,武漢430015)△Corresponding author’s e-mail,huijiexiao2@hotmail.com,zhouying0321@126.com網(wǎng)絡(luò)出版時間:2017-9-4 16:17:32網(wǎng)絡(luò)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),在服藥前及服藥后1、2、4、6、8、，

本文編號：1483675