Pharmacokinetics and safety of a new paediatric fixed-dose combination of zidovudine/lamivudine/nevirapine in HIV-infected children
Pharmacokinetics and safety of a new paediatric fixed-dose combination of zidovudine/lamivudine/nevirapine in HIV-infected children
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DOI：
10.3851/imp1931
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发表时间：
2011-01-01
影响因子：
1.2
通讯作者：
Yogev, Ram
中科院分区：
文献类型：
--
作者：
Chokephaibulkit, Kulkanya;Cressey, Tim R.;Yogev, Ram
背景资料：由于对司他夫定长期暴露的累积毒性的担忧，迅速需要替代现有的含司他夫定的儿科固定剂量复方（FDC）片剂。我们报告了一种新型儿科FDC片剂齐多夫定（ZDV）/拉米夫定（3 TC）/奈韦拉平的生物利用度和短期安全性（NVP; 30/15/28 mg）治疗HIV感染儿童。在这项I/II期开放标签药代动力学研究中，42名体重6-30 kg的儿童接受了基于NVP的HAART治疗≥ 4周，随机接受FDC片剂（GPO-VIR Z30）或液体制剂。剂量基于体重。2周后进行密集的12小时血液采样;然后将受试者交叉至相同剂量的替代制剂，并在2周后重复采样。通过非房室分析确定药代动力学参数。结果：FDC片剂对ZDV、3 TC和NVP的曲线下面积（AUC）的几何平均值（90%CI）分别为1.58（1.49-1.68）、7.78（7.38-8.19）和68.88（62.13-76.36）μ g.h/ml。NVP治疗不充分的规则是先验定义的，尽管片剂的NVP暴露量较低（P
Background: Alternatives to the available stavudine-containing paediatric fixed-dose combination (FDC) tablets are rapidly needed due to concerns regarding the cumulative toxicity of long-term stavudine exposure. We report the bioavailability and short-term safety of a novel paediatric FDC tablet of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP; 30/15/28 mg) in HIV-infected children.Methods: In this Phase I/II open-label pharmacokinetic study, 42 children weighing 6-30 kg treated with NVP-based HAART for >= 4 weeks were randomized to receive the FDC tablets (GPO-VIR Z30) or the liquid formulations. Dosing was weight-based. Intensive 12-h blood sampling was performed after 2 weeks; subjects then crossed-over to the alternate formulation at equal doses and sampling repeated 2 weeks later. Pharmacokinetic parameters were determined by non-compartmental analysis. Buccal-swab samples were collected for cytochrome P450 (CYP)2B6 polymorphism analysis.Results: With the FDC tablet, the geometric mean (90% CI) area under the curve (AUC) for ZDV, 3TC and NVP was 1.58 (1.49-1.68), 7.78 (7.38-8.19) and 68.88 (62.13-76.36) mu g.h/ml, respectively. Rules for NVP therapeutic inadequacy were defined a priori, and despite lower NVP exposure with the tablet (P