Nelfinavir pharmacokinetics in stable human immunodeficiency virus-positive children: Pediatric AIDS clinical trials group protocol 377
Nelfinavir pharmacokinetics in stable human immunodeficiency virus-positive children: Pediatric AIDS clinical trials group protocol 377
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DOI：
10.1542/peds.112.3.e220
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发表时间：
2003-09-01
期刊：
影响因子：
8
通讯作者：
Aweeka, FT
中科院分区：
文献类型：
--
作者：
Floren, LC;Wiznia, A;Aweeka, FT
Objective.从人类免疫缺陷病毒（HIV）感染儿童中获得的药代动力学数据对于在儿科人群中安全有效地使用抗逆转录病毒药物至关重要。本研究的目的是评估体重对奈非那韦（NFV）在不存在和存在奈韦拉平（NVP）的情况下的药代动力学处置的影响，并比较每日两次（BID）和每日三次（TID）NFV方案的药代动力学特征。这是一项II期、多中心、随机、开放标签试验中的密集药代动力学子研究。45例接受NFV 30 mg/kg TID治疗的HIV感染儿童和6例接受NFV 55 mg/kg BID治疗的HIV感染儿童入组本研究，并被分配至4种含司他夫定方案中的1种，3种含NFV，2种含NVP。分别测定TID和BID方案0 - 8小时（AUC（0-8小时））和0 - 12小时（AUC（0 - 12小时））的血浆浓度-时间曲线下面积。出于比较目的，还计算了每个方案的AUC 0 - 24小时。在不存在NVP的情况下，25 kg儿童的NFV暴露量降低< 25 kg compared with those who were >（中位AUC 0 - 8小时差异为2.6倍）。在NVP存在下，25 kg组之间的NFV药代动力学无差异< 25 kg and >。< 30 kg且接受NFV BID的儿童的AUC 0 - 24小时与> 25 kg且接受NFV TID的儿童的AUC 0 - 24小时相当，但比< 25 kg且接受NFV TID的儿童的AUC（0 - 24小时）大2.7倍。在没有NVP的情况下，NFV导致体重25公斤的儿童的药物暴露量不到一半< 25 kg compared with children who were >。在25 kg并接受NFV 30 mg/kg TID的儿童中以55 mg/kg BID给予NFV< 30 kg provides comparable exposure to that measured in children who are >。
Objective. Pharmacokinetic data obtained from children who have human immunodeficiency virus (HIV) infection are essential for the safe and effective use of antiretroviral agents in pediatric populations. The objective of this study was to assess the impact of body weight on the pharmacokinetic disposition of nelfinavir (NFV) in the absence and presence of nevirapine (NVP) and compare the pharmacokinetic profiles of twice-daily ( BID) and three-times-daily (TID) NFV regimens.Methods. This was an intensive pharmacokinetic substudy nested in a phase II, multicenter, randomized, open-label trial. Forty-five HIV-infected children receiving NFV 30 mg/kg TID and 6 HIV-infected children receiving NFV 55 mg/kg BID were enrolled in this study and assigned to 1 of 4 stavudine-containing regimens, 3 containing NFV and 2 containing NVP. Area under the plasma concentration-time curves from 0 to 8 hours (AUC(0-8 hours)) and from 0 to 12 hours (AUC(0 - 12 hours)) for the TID and BID regimens, respectively, were determined. For comparative purposes, the AUC0 - 24 hours was also calculated for each regimen.Results. NFV exposure in the absence of NVP was decreased in children who were < 25 kg compared with those who were > 25 kg ( a 2.6- fold difference in median AUC0 - 8 hours). NFV pharmacokinetics in the presence of NVP did not differ between the < 25 kg and > 25 kg groups. The AUC0 - 24 hours for children who were < 30 kg and on NFV BID was comparable to the AUC0 - 24 hours for children who were > 25 kg and on NFV TID but was 2.7-fold greater than AUC(0 - 24 hours) for children who were < 25 kg and on NFV TID.Conclusions. NFV in the absence of NVP resulted in less than half the drug exposure in children who were < 25 kg compared with children who were > 25 kg. NFV dosed at 55 mg/kg BID in children who are < 30 kg provides comparable exposure to that measured in children who are > 25 kg and receiving NFV 30 mg/ kg TID.