139例中国儿童AIDS病人抗病毒药物浓度监测分析  

Therapeutic drug monitoring in 139 Chinese HIV-infected children receiving HAART

作　　者：刘霞[1] 赵燕[1] 程跃武[2] 穆薇薇[1] 孙鑫[1] 窦桂芳[3] 孟志云[3] 张福杰[1] 

机构地区：[1]中国疾病预防控制中心性病艾滋病预防控制中心,北京100050 [2]河南省上蔡县疾病预防控制中心,河南上蔡463800 [3]军事医学科学院野战输血研究所,北京100850

出　　处：《中国艾滋病性病》2011年第2期103-106,151,共5页Chinese Journal of Aids & STD

基　　金：国家十一五科技重大专项(2008ZX10001-007)~~

摘　　要：目的研究中国儿童的抗病毒药物药代动力学特点,为儿童抗病毒治疗积累更多的药代动力学数据。方法收集了139名儿童艾滋病(AIDS)病人的342份血液标本,采用高效液相色谱-质谱联用的方法监测其血浆抗病毒药物的浓度。结果 139名患儿中,47名使用包含依非韦伦(EFV)的方案,94名使用包含洛匹那韦/利托那韦(LPV/r)的方案(其中2名儿童是由使用包含EFV方案更换为使用LPV/r方案)。监测药物中,EFV的个体内差异最小(15.8%),个体间差异最大(104.9%),3TC,LPV,RTV的个体内差异均在40%左右,个体间差异约为70%。以文献报道中EFV和LPV的治疗浓度范围(TR)为评判标准,在47名使用EFV的患儿中,有8名(8/47,17.0%)患儿的9份(9/115,7.8%)血标本EFV浓度低于TR,11名(11/47,23.4%)患儿的21份(21/115,18.3%)血标本EFV浓度高于TR;在94名使用LPV的患儿中,有19名(19/94,20.2%)患儿的30份(30/222,13.5%)血标本的LPV浓度低于TR,有46名(46/94,48.9%)患儿的67份(67/222,30.2%)血标本的LPV浓度高于TR。结论有相当比例的儿童艾滋病病人服用EFV和LPV/r以后出现血浆药物浓度过高,提示有必要进一步设计临床研究评估我国儿童艾滋病病人的用药剂量。血浆药物浓度监测对儿童的抗病毒治疗能够起到很好的补充作用。Objective To evaluate the pharmacokinetic characteristics of antiretroviral drugs in Chinese HIV-infected children and accumulate more pharmacokinetic data for highly active antiretroviral therapy（HAART）among Chinese children.Methods A total of 342 plasma samples were collected from 139 HIV-infected children who were receiving antiretroviral therapy.The plasma concentrations of antiretroviral drugs were measured by validated HPLC-MS method.Results Among the 139 HIV-infected children,there are 47 children receiving EFV-containing regimen,94 children receiving LPV/r-containing regimen（Two of the 94 children switched from EFV-containing regimen） EFV had a markedly higher inter-individual variability（104.9%）,but a relatively lower intra-individual variability（15.8%）.The inter-individual variability of 3TC,LPV and RTV was around 70%,whereas the intra-individual variability was around 40%.The therapeutic ranges（TR） of EFV and LPV as reported in the literature were used as a criterion of evaluating concentrations of ARV drugs.Of the 47 patients who used EFV-containing regimen,8 patients（8/47,17.0%） had 9（9/115,7.8%）blood samples with EFV concentration lower than TR,and 11 patients（11/47,23.4%）had 21（21/115,18.3%） blood samples with EFV concentration higher than TR.Of the 94 patients who used LPV/r-containing regimen,19 patients（19/94,20.2%）had 30（30/222,13.5%）blood samples with LPV concentration lower than TR,and 46 patients（46/94,48.9%） had 67（67/222,30.2%）blood samples with EFV concentration higher than TR.Conclusions Relatively high proportion of HIV-infected children experienced plasma concentration of LPV and EFV of over-therapeutic range,suggesting that it will be necessary to design prospective clinical study to evaluate whether the current dosage recommendation for EFV and LPV/r in Chinese children is overdose and whether it can cause severe adverse effects.Therapeutic drug monitoring may be used as an useful tool for clinical management of HIV-infected childre

关 键 词：儿童 艾滋病 抗病毒治疗 药物浓度监测 

分 类 号：R373.9[医药卫生—病原生物学] R512.91[医药卫生—基础医学]