Abstracts

Rationale: Rodents eliminate antiepileptic drugs (AEDs) faster than humans, creating challenges for designing clinically-relevant protocols that would result in sustained therapeutic plasma concentrations. The half-lives of AEDs in immature mice are unknown. Methods: This study examined the pharmacokinetics of commonly used AEDs in immature CD1 mice using an IP single dose protocol at post-natal day 19. Drug doses known to reach therapeutic plasma concentrations in adult rodents were administered via intraperitoneal injection. Blood draws were performed by cardiac punctures at time-points spanning 1 to 48 hours following drug administration. Additionally, brain samples were collected at 4 hours for comparison with corresponding plasma concentrations. Animal composite blood concentration versus time curves were subjected to non-compartmental analysis. Results: Plasma disappearance half lives were 2.6 hours, 15.8 hours, and 3.2 hours for Valproate, Phenobarbital, and Levetiracetam respectively, compared to 0.8 hours, 7.5 hours, and 1.5 hours in adult mice. Preliminary data for Phenytoin and Diazepam also indicate a longer half-life in immature mice than previously reported for adult rodents. Corresponding drug concentrations in brain samples are being evaluated to discern blood brain barrier access. Conclusions: All drugs tested had longer half-lives and maintained therapeutic plasma concentrations for periods longer than reported in mature mice.