A Phase I/II Study of the Protease Inhibitor Ritonavir in Children With Human Immunodeficiency Virus Infection
A Phase I/II Study of the Protease Inhibitor Ritonavir in Children With Human Immunodeficiency Virus Infection
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蛋白酶抑制剂利托那韦治疗人类免疫缺陷病毒感染儿童的 I/II 期研究
DOI：
10.1542/peds.101.3.335
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发表时间：
1998
期刊：
影响因子：
8
通讯作者：
P. Pizzo
中科院分区：
文献类型：
--
作者：
B. Mueller;R. Nelson;J. Sleasman;J. Zuckerman;M. Heath;S. Steinberg;F. Balis;P. Brouwers;A. Hsu;Rima Saulis;S. Sei;L. Wood;S. Zeichner;T. Katz;Colleen Higham;Diane Aker;M. Edgerly;P. Jarosinski;L. Serchuck;S. Whitcup;D. Pizzuti;P. Pizzo
背景。 利托那韦是一种有效的抗逆转录病毒蛋白酶抑制剂，已被批准用于治疗人类免疫缺陷病毒（HIV）感染的成人和儿童。在一项 I/II 期研究中，我们评估了利托那韦口服溶液在 HIV 感染儿童中的安全性、耐受性和药代动力学特征，并研究了初步抗病毒和临床效果。方法。 6 个月至 18 岁之间的 HIV 感染儿童符合资格。在两个年龄组（≤2 岁、>2 岁）中评估利托那韦口服溶液的四种剂量水平（每 12 小时给予 250、300、350 和 400 mg/m2）。利托那韦在前 12 周单独给药，然后与齐多夫定和/或去羟肌苷联合给药。每 2 至 4 周监测一次临床和实验室参数。结果。 本次分析共有 48 名儿童（中位年龄 7.7 岁；范围 0.5 至 14.4 岁）。与剂量相关的恶心、腹泻和腹痛是最常见的毒性，导致 7 名儿童停用利托那韦。利托那韦在所有剂量水平下均被良好吸收，血浆浓度在给药后 2 至 4 小时达到峰值。单药治疗 4 周后，CD4 细胞计数中位数增加了 79 个细胞/mm3，并在整个研究过程中保持不变。利托那韦单药治疗 4 至 8 周内，血浆 HIV RNA 下降 1 至 2 log10 拷贝/mL，并且在 24 周内以 400 mg/m2 最高剂量水平入组的患者中，这一水平得以维持。结论。 利托那韦口服溶液作为单一药物具有有效的抗逆转录病毒活性，并且当单独给药或与齐多夫定或去羟肌苷联合给药时，儿童的耐受性相对良好。
Background. Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. Methods. HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m2 given every 12 hours) were evaluated in two age groups (≤2 years, >2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. Results. A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m2 for the 24-week period. Conclusions. The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.
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影响因子：
158.5
作者：
Collier, AC;Coombs, RW;Corey, L
通讯作者：
Corey, L
DOI：
10.1056/nejm199512073332204
发表时间：
1995-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
M. Markowitz;M. Saag;W. Powderly;A. Hurley;A. Hsu;J. Valdes;D. Henry;F. Sattler;Anthony F. La Marca;J. Leonard;D. Ho
通讯作者：
M. Markowitz;M. Saag;W. Powderly;A. Hurley;A. Hsu;J. Valdes;D. Henry;F. Sattler;Anthony F. La Marca;J. Leonard;D. Ho
司他夫定和去羟肌苷联合治疗晚期人类免疫缺陷病毒感染儿童：药代动力学特性、安全性以及免疫学和病毒学效应。
影响因子：
8
作者：
Kline,MW;Fletcher,CV;Federici,ME;Harris,AT;Evans,KD;Rutkiewicz,VL;Shearer,WT;Dunkle,LM
通讯作者：
Dunkle,LM
通过基于聚合酶链反应的检测对人类免疫缺陷病毒感染的婴儿进行病毒测量。
DOI：
10.1016/s0022-3476(95)70357-8
发表时间：
1995
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Palumbo,PE;Kwok,S;Waters,S;Wesley,Y;Lewis,D;McKinney,N;Bardeguez,A;Connor,EM;Oleske,JM
通讯作者：
Oleske,JM