Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, UAB, Birmingham, AL, USA.
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA.
Pulm Pharmacol Ther. 2024 Sep;86:102301. doi: 10.1016/j.pupt.2024.102301. Epub 2024 May 24.
Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.
依伐卡托、泰它卡托、艾美卡替（ETI）是一种 CFTR 调节剂组合，已批准用于 2 岁以上约 90%的囊性纤维化（CF）患者。尽管大多数 CF 患者对这种治疗耐受良好，但有些患者对标准剂量不耐受，有些患者反应甚微。临床医生可能会调整 ETI 剂量以解决这些问题，但这些调整并没有得到药代动力学证据的很好指导。我们的上市后研究旨在描述 15 名接受标准或降低剂量的参与者的 ETI 血浆浓度的药代动力学变异性。在早上给药前采集血浆样本，通过 LC-MS/MS 定量 ETI。结果显示，无论剂量方案如何，每种化合物均无显著差异，且在剂量等效归一化后也无显著差异。两个剂量组的大多数参与者的浓度都有望对 ETI 治疗产生临床反应。这些发现表明，减少剂量可能是一种可行的策略，可在管理不耐受的同时保持临床获益。
