REFINING PRECLINICAL ANTISEIZURE DRUG DOSING: A WELFARE-FRIENDLY, CLINICALLY RELEVANT ORAL DELIVERY PLATFORM

Epilepsy affects over 65 million people worldwide, with antiseizure medications (ASMs) as the primary treatment. In preclinical epilepsy research, ASMs are commonly administered via acute intraperitoneal (IP) injection, often at full target dose. This approach has important limitations: repeated IP injections cause stress and welfare concerns, and acute bolus dosing poorly reflects clinical practice, where ASMs are gradually titrated to achieve therapeutic concentrations while minimising adverse effects.
We aimed to develop and validate a refined, welfare-friendly chronic ASM dosing method in rodents that achieves clinically relevant blood and brain drug concentrations while allowing dose titration.
Rodents received human-scaled doses of two commonly prescribed ASMs, lamotrigine and topiramate, either by standard IP injection or via voluntary oral ingestion using a flavoured jelly formulation. Animals readily consumed the medicated jelly without handling or restraint. Blood and brain tissue were collected at defined time points, and drug concentrations were quantified using mass spectrometry.
Preliminary pharmacokinetic analyses showed that both administration routes achieved plasma concentrations within the human therapeutic range for lamotrigine and topiramate. Oral jelly-based dosing produced plasma and brain drug levels comparable to IP injection, with concentrations—particularly for topiramate—remaining within the therapeutic range for longer than anticipated, supporting feasibility for repeated or chronic dosing.
Voluntary oral administration of ASMs using flavoured jelly provides a welfare-refined, titration-based alternative to IP injection while maintaining clinically relevant systemic exposure. This approach better reflects clinical practice and may enhance the translational validity of preclinical epilepsy research in terms of ASM efficacy and adverse effects.