Kline M W, Blanchard S, Fletcher C V, Shenep J L, McKinney R E, Brundage R C, Culnane M, Van Dyke R B, Dankner W M, Kovacs A, McDowell J A, Hetherington S
Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
Pediatrics. 1999 Apr;103(4):e47. doi: 10.1542/peds.103.4.e47.
To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretroviral agents, in symptomatic human immunodeficiency virus (HIV)-infected children.
HIV-infected children discontinued prior antiretroviral therapy and were given abacavir orally, 4 mg/kg every 12 hours for 6 weeks, followed by 8 mg/kg every 12 hours for 6 weeks (n = 39); or 8 mg/kg every 12 hours for 12 weeks (n = 8). Children then were randomized to receive a second nucleoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudine), plus abacavir. Pharmacokinetics, safety, tolerance, CD4(+) lymphocyte counts, and plasma HIV RNA concentrations were evaluated.
At a dose of 8 mg/kg every 12 hours, area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily. One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy. Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent. Mean CD4(+) lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy.
Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children. Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults.
评估阿巴卡韦单独使用以及与其他核苷类抗逆转录病毒药物联合使用时，对有症状的人类免疫缺陷病毒（HIV）感染儿童的药代动力学特征、安全性和耐受性。
HIV感染儿童停用先前的抗逆转录病毒疗法，口服阿巴卡韦，每12小时4mg/kg，共6周，随后每12小时8mg/kg，共6周（n = 39）；或每12小时8mg/kg，共12周（n = 8）。然后将儿童随机分组，接受第二种核苷类抗逆转录病毒药物（齐多夫定、司他夫定、去羟肌苷或拉米夫定）加阿巴卡韦治疗。评估药代动力学、安全性、耐受性、CD4(+)淋巴细胞计数和血浆HIV RNA浓度。
每12小时8mg/kg剂量时，血浆浓度-时间曲线下面积和血浆半衰期值与每日两次接受300mg阿巴卡韦治疗的成人报告值相当。阿巴卡韦单药治疗期间分别发生1例过敏反应和1例周围神经病变。3名儿童在接受阿巴卡韦与另一种抗逆转录病毒药物联合治疗时出现中性粒细胞减少。当先前的抗逆转录病毒疗法改为阿巴卡韦单药治疗时，平均CD4(+)淋巴细胞计数和血浆HIV RNA浓度未发生变化。
阿巴卡韦治疗对HIV感染儿童具有良好的短期耐受性和安全性。正在进行III期研究以评估阿巴卡韦在儿童和成人中的抗病毒活性。
