通用型儿科多替拉韦分散片在体重低于20公斤的泰国感染艾滋病毒幼儿中的药代动力学

Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms.

作者信息

Rungsapphaiboon Athiporn, Wacharachaisurapol Noppadol, Anugulruengkitt Suvaporn, Sirikutt Pugpen, Phasomsap Chayapa, Tawan Monta, Saisaengjan Chutima, Na Nakorn Yossawadee, Paiboon Nantika, Songtaweesin Wipaporn Natalie, Tawon Yardpiroon, Cressey Tim R, Puthanakit Thanyawee

机构信息

From the Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Department of Pediatrics, Khon Kaen Hospital, Khon Kaen, Thailand.

出版信息

Pediatr Infect Dis J. 2024 Aug 1;43(8):789-794. doi: 10.1097/INF.0000000000004366. Epub 2024 May 17.

DOI:10.1097/INF.0000000000004366

PMID:39018516

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11250107/

Abstract

INTRODUCTION

Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic responses of generic DTG-DT in children weighing <20 kg.

METHODS

Children living with HIV-1 and <7 years of age weighing 6 to <20 kg were eligible. A generic 10-mg scored DTG-DT was administered to children using 3 weight bands (WB): WB1 (6 to <10 kg), WB2 (10 to <14 kg) and WB3 (14 to <20 kg), at doses of 20 mg (higher than World Health Organization recommendation of 15 mg), 20 mg and 25 mg, respectively. Steady-state intensive pharmacokinetics (PK) was performed in fasting condition with blood sampling at predose and 1, 2, 3, 4, 6 and 24 hours postdose. DTG PK parameters were estimated using a noncompartmental analysis, and DTG trough concentrations (C 24 ) and 24-hour area under the concentration-time curve were calculated. Comparisons were made with ODYSSEY and IMPAACT 2019. And 90% effective concentration of 0.32 mg/L was used as a reference individual DTG C 24 concentration.

RESULTS

From August 2021 to March 2023, 29 Thai children with a median (interquartile range) age of 3.2 (1.5-4.8) years were enrolled; 8 in WB1, 9 in WB2 and 12 in WB3. All children were treatment experienced and 59% had HIV RNA <200 copies/mL. Overall geometric mean (coefficient of variation percentage) DTG C 24 was 1.0 (46%) mg/L [WB1, 0.9 (53%); WB2, 0.9 (27%); WB3, 1.2 (51%)]. Geometric mean (coefficient of variation percentage) 24-hour area under the concentration-time curve was 83.2 (24%) mg h/L [WB1, 84.3 (31%); WB2, 76.9 (16%); WB3, 87.6 (25%)]. At weeks 24 and 48, 90% and 92% of participants had plasma HIV RNA <200 copies/mL.

CONCLUSIONS

Generic DTG-DT provided adequate drug exposure in children weighing 6 to <20 kg. The exploratory dose of DTG 20 mg for children weighing 6 to <10 kg showed similar PK parameters to World Health Organization doses in the other WB.

摘要

引言

多替拉韦（DTG）分散片（DTG-DT）是一种适合儿童使用的剂型。我们旨在描述通用型DTG-DT在体重<20千克儿童中的药代动力学和病毒学反应。

方法

年龄<7岁、体重6至<20千克的HIV-1感染儿童符合入选标准。使用3个体重分组（WB）给儿童服用通用型10毫克刻痕DTG-DT：WB1（6至<10千克）、WB2（10至<14千克）和WB3（14至<20千克），剂量分别为20毫克（高于世界卫生组织推荐的15毫克）、20毫克和25毫克。在禁食状态下进行稳态强化药代动力学（PK）研究，给药前及给药后1、2、3、4、6和24小时采集血样。使用非房室分析估计DTG的PK参数，并计算DTG谷浓度（C24）和浓度-时间曲线下的24小时面积。与ODYSSEY和IMPAACT 2019进行比较。以0.32毫克/升的90%有效浓度作为个体DTG C24浓度的参考值。

结果

2021年8月至2023年3月，纳入29名泰国儿童，中位（四分位间距）年龄为3.2（1.5 - 4.8）岁；WB1组8名，WB2组9名，WB3组12名。所有儿童均有治疗史，59%的儿童HIV RNA<200拷贝/毫升。总体DTG C24几何均值（变异系数百分比）为1.0（46%）毫克/升[WB1组，0.9（53%）；WB2组，0.9（27%）；WB3组，1.2（51%）]。浓度-时间曲线下24小时面积的几何均值（变异系数百分比）为83.2（24%）毫克·小时/升[WB1组，84.3（31%）；WB2组，76.9（16%）；WB3组，87.6（25%）]。在第24周和第48周，90%和92%的参与者血浆HIV RNA<200拷贝/毫升。