盖伦制剂改良作为口服抗癌药物给药的替代策略：生物等效性评估

文献信息

中文摘要

背景： 口服抗癌药物已被广泛使用，提高了患者的自主性和生活质量。然而，吞咽障碍患者，如儿童、老年人以及头颈癌或神经系统疾病患者，常需要盖伦制剂改良（例如压碎药片、口服混悬液），这可能影响药物药代动力学和临床结局。
目的： 本研究旨在评估这些改良对生物等效性和全身药物暴露的影响。
方法： 对96种口服抗癌药物的监管文件和科学文献进行了系统性研究。收集了标准口服固体剂型与替代性操作或液体制剂之间的生物等效性或相对生物利用度数据。评估了药物的化学和药学性质作为生物等效性的预测因素。
结果： 在入选研究的96种药物中，有39种药物可获得数据。26种药物的液体制剂未达到完全生物等效性标准：最大血浆浓度（Cmax）比曲线下面积（AUC）更常发生改变，提示盖伦制剂改良主要影响吸收速率而非总体药物暴露。然而，在83%的病例中，AUC比值保持在0.5至2之间。未发现生物等效性的预测因素。
结论： 抗癌药物的液体制剂和盖伦制剂改良主要增加药物暴露，尤其是Cmax。由于盖伦制剂改良的药代动力学影响较低且不可预测，无法推荐先验剂量调整。因此，在可能的情况下需要进行治疗药物监测，并且操作应在监督和标准化条件下进行。

英文摘要

BACKGROUND: Oral anticancer drugs have become widely used, improving patient autonomy and quality of life. However, patients with swallowing disorders, such as children, older adults, and patients with head and neck cancer or neurologic disease, often require galenic modifications (e.g., crushed tablets, oral suspensions) that may impact drug pharmacokinetics and clinical outcomes.
OBJECTIVE: The aim of this study was to assess the impact of these modifications on bioequivalence and systemic drug exposure.
METHODS: A systematic research of regulatory documents and scientific literature was conducted on 96 oral anticancer drugs. Data were collected on bioequivalence or relative bioavailability between standard oral solid forms and alternative manipulated or liquid formulations. Chemical and pharmaceutical properties of drugs were assessed as predictive factors for bioequivalence.
RESULTS: Data were available for 39 drugs among the 96 selected for the study. The liquid form of 26 drugs did not meet full bioequivalence criteria: maximum plasma concentration (Cmax) was more frequently altered than area under the curve (AUC), suggesting that galenic modification primarily affected the absorption rate rather than overall drug exposure. Nevertheless, in 83% of cases, AUC ratios remained between 0.5 and 2. No predictive factors of bioequivalence were identified.
CONCLUSION: Liquid formulation and galenic modification of anticancer drugs primarily increases drug exposure, especially Cmax. A priori dose adjustments could not be recommended due to the low and unpredictable pharmacokinetic impact of galenic modifications. Consequently, therapeutic drug monitoring is required when possible, and manipulation should be performed under supervised and standardized conditions.