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Neuroreport. 2010 Apr 21;21(6):452-6.

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

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1
Department of Neurology and Developmental Medicine, Kennedy Krieger Research Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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.

PMID:
20848732
PMCID:
PMC3220279
[Indexed for MEDLINE]
Free PMC Article
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