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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 study the pharmacokinetics of antiviral drugs in Chinese children and to accumulate more pharmacokinetic data for children antiviral therapy. Methods A total of 342 blood samples from 139 children with AIDS were collected and their plasma anti-viral concentrations were monitored by high performance liquid chromatography-mass spectrometry. Results Of the 139 children, 47 received efavirenz (EFV) -based regimens and 94 received lopinavir / ritonavir (LPV / r) regimens EFV program was changed to use the LPV / r program). Among the monitored drugs, EFV had the lowest intraspecific difference (15.8%), the highest inter-individual difference (104.9%), and the individual differences of 3TC, LPV and RTV were about 40% and the inter-individual differences were about 70%. According to the treatment concentration range (TR) of EFV and LPV reported in the literature, there were 9 out of 47 children (9 / 115,7.8 %). The EFV concentration in 21 (21/115, 18.3%) blood samples of 11 (11/47, 23.4%) children with blood samples with EFV lower than that of TR was higher than that of TR. In 94 children with LPV Thirty (30 / 222,13.5%) blood samples of 19 (19/94, 20.2%) children had LPV concentrations lower than TR, and 46 (46/94, 48.9%) of 46 children (67 / 222,30.2%) blood samples LPV concentration higher than TR. Conclusion A considerable proportion of children with AIDS patients taking EFV and LPV / r after the emergence of high concentrations of plasma drugs, suggesting the need for further design of clinical studies to assess the dosage of children with AIDS in our country. Plasma drug concentration monitoring can be a good complement to children’s antiviral therapy.