Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.
Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.
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DOI：
10.1183/13993003.01596-2022
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发表时间：
2023-03
影响因子：
24.3
通讯作者：
Alffenaar, Jan-Willem C.
中科院分区：
文献类型：
--
作者：
Gafar, Fajri;Wasmann, Roeland E.;McIlleron, Helen M.;Aarnoutse, Rob E.;Schaaf, H. Simon;Marais, Ben J.;Agarwal, Dipti;Antwi, Sampson;Bang, Nguyen D.;Bekker, Adrie;Bell, David J.;Chabala, Chishala;Choo, Louise;Davies, Geraint R.;Day, Jeremy N.;Dayal, Rajeshwar;Denti, Paolo;Donald, Peter R.;Engidawork, Ephrem;Garcia-Prats, Anthony J.;Gibb, Diana;Graham, Stephen M.;Hesseling, Anneke C.;Heysell, Scott K.;Idris, Misgana I.;Kabra, Sushil K.;Kinikar, Aarti;Kumar, Agibothu K. Hemanth;Kwara, Awewura;Lodha, Rakesh;Magis-Escurra, Cecile;Martinez, Nilza;Mathew, Binu S.;Mave, Vidya;Mduma, Estomih;Mlotha-Mitole, Rachel;Mpagama, Stellah G.;Mukherjee, Aparna;Nataprawira, Heda M.;Peloquin, Charles A.;Pouplin, Thomas;Ramachandran, Geetha;Ranjalkar, Jaya;Roy, Vandana;Ruslami, Rovina;Shah, Ira;Singh, Yatish;Sturkenboom, Marieke G. G.;Svensson, Elin M.;Swaminathan, Soumya;Thatte, Urmila;Thee, Stephanie;Thomas, Tania A.;Tikiso, Tjokosela;Touw, Daan J.;Turkova, Anna;Velpandian, Thirumurthy;Verhagen, Lilly M.;Winckler, Jana L.;Yang, Hongmei;Yunivita, Vycke;Taxis, Katja;Stevens, Jasper;Alffenaar, Jan-Willem C.
抗结核药物的次优暴露与不利的治疗结果有关。我们的目的是调查全球范围内儿童和青少年一线抗结核药物药代动力学的估计值和决定因素。系统检索MEDLINE、Embase和Web of Science（1990-2021）中有关儿童和青少年一线抗结核药物的药代动力学研究。个体患者数据来自合格研究的作者。使用随机效应模型评估给药后0 - 24 h的总/外推血药浓度-时间曲线下面积（AUC 0 -24）和血药峰浓度（Cmax）的汇总估计值，并使用当前世界卫生组织推荐的儿科剂量进行标准化。采用线性混合效应模型评估AUC 0 -24和Cmax的决定因素。在55项合格研究中，39项（71%）的个体患者数据可用，包括来自12个国家的1628名参与者。总结了异烟肼（18.7（95% CI 15.5-22.6）h·mg·L−1）、利福平（34.4（95% CI 29.4-40.3）h·mg·L − 1）、吡嗪酰胺（375.0（95% CI 339.9-413.7）h·mg·L−1）和乙胺丁醇（8.0（95% CI 6.4-10.0）h·mg·L−1）稳态AUC 0 -24的几何平均值。 我们的多变量模型表明，年龄较小（特别是<2岁）和HIV阳性状态与所有一线抗结核药物的AUC 0 -24较低相关，而严重营养不良与异烟肼和吡嗪酰胺的AUC 0 -24较低相关。 与中间乙酰化酶相比，N-乙酰转移酶2快速乙酰化酶的异烟肼AUC 0 -24较低，慢速乙酰化酶的异烟肼AUC 0 -24较高。Cmax的决定因素通常与AUC 0 -24的决定因素相似。这项研究提供了对儿童和青少年一线抗结核药物血浆暴露的最全面估计。确定了药物暴露的关键决定因素。这些可能与人群特异性剂量调整或个体化治疗药物监测相关。根据全球现有数据评估了儿童和青少年抗结核药物药代动力学的汇总估计值和关键决定因素，倡导在某些暴露风险低于最佳水平的人群中调整剂量或监测治疗药物https://bit.ly/3Vzw4f0
Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. We systematically searched MEDLINE, Embase and Web of Science (1990–2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration–time curve from 0 to 24 h post-dose (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0–24 and Cmax were assessed with linear mixed-effects models. Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0–24 were summarised for isoniazid (18.7 (95% CI 15.5–22.6) h·mg·L−1), rifampicin (34.4 (95% CI 29.4–40.3) h·mg·L−1), pyrazinamide (375.0 (95% CI 339.9–413.7) h·mg·L−1) and ethambutol (8.0 (95% CI 6.4–10.0) h·mg·L−1). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC0–24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0–24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0–24 and slow acetylators had higher isoniazid AUC0–24 than intermediate acetylators. Determinants of Cmax were generally similar to those for AUC0–24. This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring. Summary estimates and key determinants of anti-TB drug pharmacokinetics in children and adolescents were assessed from globally available data, advocating for dose adjustment or therapeutic drug monitoring in certain groups at risk of suboptimal exposures https://bit.ly/3Vzw4f0
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影响因子：
24.3
作者：
Gafar，Fajri;van't Boveneind-Vrubleuskaya，Natasha;Alffenaar，Jan-Willem C.
通讯作者：
Alffenaar，Jan-Willem C.
影响因子：
2.9
作者：
Azuma, Junichi;Ohno, Masako;Kubota, Ryuji;Yokota, Soichiro;Nagai, Takayuki;Tsuyuguchi, Kazunari;Okuda, Yasuhisa;Takashima, Tetsuya;Kamimura, Sayaka;Fujio, Yasushi;Kawase, Ichiro
通讯作者：
Kawase, Ichiro
影响因子：
2.5
作者：
Kim HY;Byashalira KC;Heysell SK;Märtson AG;Mpagama SG;Rao P;Sturkenboom MGG;Alffenaar JC
通讯作者：
Alffenaar JC
影响因子：
5.2
作者：
Dayal, Rajeshwar;Singh, Yatish;Kumar, A. K. Hemant
通讯作者：
Kumar, A. K. Hemant
影响因子：
11.8
作者：
Alffenaar, Jan-Willem C.;Gumbo, Tawanda;Migliori, Giovanni Battista
通讯作者：
Migliori, Giovanni Battista