The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice.

TitleThe pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice.
Publication TypeJournal Article
Year of Publication2010
AuthorsMarkowitz GJ, Kadam SD, Boothe DM, Irving ND, Comi AM
JournalNeuroreport
Volume21
Issue6
Pagination452-6
Date Published2010 Apr 21
Abstract

Rodents eliminate antiepileptic drugs (AEDs) faster than humans, creating challenges for designing clinically relevant protocols. Half-lives of AEDs in immature mice are unknown. The pharmacokinetics of commonly used AEDs were examined in CD1 mice using a single-dose protocol at postnatal day 19. After intraperitoneal therapeutic dosing, blood serum concentrations spanning 1-48 h post-administration and corresponding brain tissue concentrations at 4 h were analyzed. Half-lives of valproate, phenobarbital, diazepam (and metabolites), phenytoin, and levetiracetam were 2.6, 15.8, 22.3, 16.3, and 3.2 h, respectively, compared to 0.8, 7.5, 7.7, 16.0, and 1.5 h reported for adult mice. Brain-to-blood ratios were comparable with adult ratios. AEDs tested had longer half-lives and maintained therapeutic plasma concentrations longer than reported in mature mice, making clinically relevant protocols feasible.

DOI10.1097/BRS.0b013e3181e7d675
Alternate JournalNeuroreport