Galenic Modification as an Alternative Strategy for Administering Oral Anticancer Drugs: Assessment of Bioequivalence.

Abstract

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 (C_max) 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 C_max. 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.