From the *Department of Pediatrics, University of Padua, Italy; †Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone, Botswana; ‡Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Germany; §Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa; ¶Tati River Clinic, Francistown, Botswana; ‖Department of Pediatrics, Goethe University, Frankfurt, Germany; and **Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT.
Pediatr Infect Dis J. 2014 Jul;33(7):e173-9. doi: 10.1097/INF.0000000000000241.
To compare steady-state (ss) pharmacokinetic targets of nevirapine extended-release (NVP-XR) tablets once-daily (QD) with immediate-release (NVP-IR) tablet or oral suspension twice-daily in HIV-1-infected children and adolescents.
Phase I, open-label, multidose, cross-over study with optional extension phase, in 85 patients 3 to <18 years of age, previously on an NVP-IR-based regimen for ≥18 weeks with baseline viral load <50 copies/mL. Patients were stratified by age, treated with NVP-IR twice-daily for 11 days, then NVP-XR QD for 10 days. Cpre,ss (steady-state, predose concentrations) was obtained from all, and 12-hour NVP-IR and 24-hour NVP-XR steady-state pharmacokinetic profiles were obtained in the pharmacokinetic substudy. Viral loads, CD4 counts and adverse events (AEs) were monitored.
Eighty patients completed the trial. Adjusted geometric mean (gMean) Cpre,ss for NVP-XR and NVP-IR exceeded the target of 3000 ng/mL, and the adjusted gMean NVP-XR:NVP-IR ratio (90% confidence interval) for QD normalized and un-normalized Cpre,ss were 91.2% (83.5-99.6%) and 91.8% (83.7-100.7%). gMean 24-hour area under the curve at steady-state NVP-XR:NVP-IR for un-normalized dose was 90.4% and un-normalized Cpre,ss NVP-XR:NVP-IR were 91.0%, 81.9% and 103.7% for the 3 age groups, 3 to <6, 6 to <12 and 12 to <18 years, respectively. gMean values indicated no exposure to subtherapeutic NVP concentrations and viral suppression was adequate and maintained in all QD groups. Most AEs were mild and similar between age groups. No serious or Division of AIDS Grade 4 AEs or AE related treatment discontinuations occurred.
NVP-XR exhibited adequate trough concentrations with equivalent area under the curve at steady-state relative to NVP-IR. NVP-XR was well-tolerated and is a valuable treatment option for HIV-infected children and adolescents.
比较每日一次服用奈韦拉平（NVP）延长释放片（NVP-XR）与每日两次服用即刻释放片（NVP-IR）或口服混悬剂在 HIV-1 感染的儿童和青少年中的稳态（ss）药代动力学目标。
这项 I 期、开放标签、多剂量、交叉研究包括可选的扩展阶段，共纳入 85 名年龄 3 至<18 岁、基线病毒载量<50 拷贝/ml、之前接受基于 NVP-IR 方案治疗≥18 周的患者。根据年龄对患者进行分层，每日两次接受 NVP-IR 治疗 11 天，然后每日一次接受 NVP-XR 治疗 10 天。所有患者均获得 Cpre,ss（稳态、预剂量浓度），并在药代动力学亚研究中获得 12 小时 NVP-IR 和 24 小时 NVP-XR 稳态药代动力学曲线。监测病毒载量、CD4 计数和不良事件（AE）。
80 名患者完成了试验。NVP-XR 和 NVP-IR 的调整后几何均数（gMean）Cpre,ss 超过了 3000ng/ml 的目标，QD 标准化和未标准化 Cpre,ss 的调整后 gMean NVP-XR：NVP-IR 比值（90%置信区间）分别为 91.2%（83.5-99.6%）和 91.8%（83.7-100.7%）。未标准化剂量时，稳态 NVP-XR：NVP-IR 的 24 小时 AUC 调整后 gMean 为 90.4%，未标准化 Cpre,ss 的 NVP-XR：NVP-IR 比值分别为 91.0%、81.9%和 103.7%，分别为 3 个年龄组（3 至<6、6 至<12 和 12 至<18 岁）。gMean 值表明未出现低于治疗浓度的 NVP 浓度，所有 QD 组的病毒抑制均充分且维持。大多数 AE 为轻度，且各年龄组之间相似。未发生严重或艾滋病分期 4 级 AE 或与 AE 相关的治疗中断。
NVP-XR 表现出与 NVP-IR 相当的稳态谷浓度和 AUC。NVP-XR 耐受性良好，是治疗 HIV 感染儿童和青少年的一种有价值的选择。
