Venetoclax Clinical Pharmacokinetics After Administration of Crushed, Ground or Whole Tablets

IF 3.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics Pub Date : 2024-10-01 DOI:10.1016/j.clinthera.2024.03.012

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引用次数: 0

Abstract

Purpose

Venetoclax is a potent, orally bioavailable BCL-2 inhibitor used in the treatment of some hematological malignancies. Crushing tablets may be necessary to help with the administration of venetoclax to patients with swallowing difficulties or patients requiring nasogastric tube feeding. The study was conducted to assess the bioavailability of crushed and finely ground venetoclax tablets relative to whole tablets.

Methods

An open-label, randomized, 3-way, crossover study in 15 healthy adult females was conducted. Venetoclax tablets were administered orally in a crushed, ground or intact form on Day 1 of each period with water following a high-fat breakfast. Pharmacokinetic samples were collected up to 72 hours postdosing.

Findings

The crushed and ground tablets met the bioequivalence criteria (0.80–1.25) relative to the intact tablets with respect to area under the concentration-time curve to time of the last measurable concentration (AUC_t) and to infinite time (AUC_inf) but exhibited a slightly lower maximum plasma concentration (C_max). This was not considered clinically significant as only venetoclax overall exposure (AUC) has been shown to correlate with clinical efficacy. There was no change in the physical appearance and the evaluated physicochemical properties of crushed and ground venetoclax tablets after 72 hours of storage at 25°C/60% relative humidity.

Implications

Crushing or grinding venetoclax tablets before administration could be considered as a viable alternative method of administration for patients who have difficulty swallowing whole venetoclax tablets or patients requiring nasogastric tube feeding.

ClinicalTrials.gov identifiers

NCT05909553, registered June 12, 2023.

查看原文本刊更多论文

服用碾碎、研磨或整片药片后的 Venetoclax 临床药代动力学。

目的：Venetoclax 是一种强效、口服生物利用度高的 BCL-2 抑制剂，用于治疗某些血液恶性肿瘤。为了帮助吞咽困难的患者或需要鼻胃管喂养的患者服用 Venetoclax，可能需要将药片碾碎。本研究旨在评估与整片药片相比，碾碎和磨细的 Venetoclax 片剂的生物利用度：方法：在15名健康成年女性中开展了一项开放标签、随机、三向交叉研究。在每个研究阶段的第 1 天，在高脂早餐后用水口服压碎、磨碎或完整的 Venetoclax 片剂。用药后 72 小时内采集药代动力学样本：与完整片剂相比，粉碎片剂和研磨片剂在最后可测量浓度时间曲线下面积（AUCt）和无限时间曲线下面积（AUCinf）方面符合生物等效性标准（0.80-1.25），但最大血浆浓度（Cmax）略低。由于只有 Venetoclax 的总体暴露量（AUC）被证明与临床疗效相关，因此这并不具有临床意义。在 25°C/60% 相对湿度条件下贮存 72 小时后，碾碎和磨碎的 Venetoclax 药片的物理外观和所评估的理化性质均无变化：意义：对于难以吞咽整片venetoclax片剂的患者或需要鼻胃管喂养的患者，在给药前粉碎或研磨venetoclax片剂可被视为一种可行的替代给药方法：Gov 标识符：NCT05909553，2023年6月12日注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical therapeutics 医学-药学

CiteScore

6.00

自引率

3.10%

发文量

154

审稿时长

9 weeks

期刊介绍： Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.