Ivacaftor, Tezacaftor, elexaftor和Lumacaftor在特殊囊性纤维化人群中的药代动力学:一项系统综述。

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Clinical Pharmacokinetics Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI:10.1007/s40262-025-01507-2
Femke A Elzinga, Paul R V Malik, Onno W Akkerman, Bart L Rottier, Hester van der Vaart, Daan J Touw, Gerard H Koppelman, Paola Mian
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引用次数: 0

摘要

背景与目的:随着囊性纤维化跨膜传导调节剂(ivacaftor, tezacaftor, elexaftor和lumacaftor)的发展,囊性纤维化(pwCF)患者的预后得到改善。了解CFTR调节剂的药代动力学(PK)对于提供最佳护理至关重要,特别是在特殊的囊性纤维化(CF)人群中,如肝功能损害、胰腺功能不全、怀孕或哺乳期或儿童的pwCF患者。我们的目的是概述CFTR调制器在这些人群中的PK。方法:于2024年6月20日在PubMed和Embase进行系统文献检索。当有关于PK或cftr调节药物暴露的信息时,研究被认为是相关的。结果:轻度/中度肝功能损害的PwCF与无肝损害或健康个体相比,CFTR调节剂暴露量并未显著增加。同样,外分泌胰功能不全对成人pwCF中CFTR调节剂的PK没有影响。相比之下,与成人相比,儿童pwCF暴露于更高水平的CFTR调节剂,因为儿童接受更高的基于体重的剂量(mg/kg)以确保同等的治疗效果。结论:CFTR调节剂的PK在成人、轻度/中度肝功能损害的pwCF和儿童中得到了更广泛的研究。然而,确保足够的剂量仍然具有挑战性。对于严重肝功能损害的成人(Child-Pugh Class C)、cf所致肝功能损害的儿童以及妊娠期或哺乳期pwCF患者,知识差距仍然存在。通过纳入常规临床数据,解决这些差距的未来研究对于改进临床指南和优化给药方案至关重要,从而朝着循证利用CFTR调节剂的方向发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacokinetics of Ivacaftor, Tezacaftor, Elexacaftor, and Lumacaftor in Special Cystic Fibrosis Populations: A Systematic Review.

Background and objective: Following the development of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (ivacaftor, tezacaftor, elexacaftor, and lumacaftor), the prognosis for people diagnosed with cystic fibrosis (pwCF) has improved. Understanding the pharmacokinetics (PK) of CFTR modulators is crucial to provide optimal care, particularly in special cystic fibrosis (CF) populations such as pwCF with hepatic impairment, pancreatic insufficiency, those who are pregnant or lactating, or who are children. We aim to provide an overview of the PK of CFTR modulators in these populations.

Methods: A systematic literature search was carried out in PubMed and Embase on 20 June 2024. Studies were considered relevant when information on PK or exposure of CFTR-modulating drugs was available.

Results: PwCF with mild/moderate hepatic impairment do not exhibit substantially higher exposure to CFTR modulators compared with those without liver involvement or healthy individuals. Similarly, exocrine pancreatic insufficiency has no effect on the PK of CFTR modulators in adult pwCF. In contrast, pediatric pwCF are exposed to higher levels of CFTR modulators relative to adults, as children receive higher weight-based doses (mg/kg) to ensure equivalent therapeutic efficacy.

Conclusions: The PK of CFTR modulators have been more extensively studied in adults, pwCF with mild/moderate hepatic impairment, and children. However, ensuring adequate dosing remains challenging. Knowledge gaps persist for adults with severe hepatic impairment (Child-Pugh Class C), children with CF-induced hepatic impairment, and pregnant or lactating pwCF. Future research addressing these gaps, through incorporating routine clinical data, is crucial for improving clinical guidelines and optimizing dosing regimens, thereby advancing towards evidence-based utilization of CFTR modulators.

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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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