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

Mark McIntosh,'s picture
PubMed URL: 
http://www.ncbi.nlm.nih.gov/pubmed/20848732
Author: 
Comi AM
Author List: 
Markowitz GJ
Kadam SD
Boothe DM
Irving ND
Comi AM
Journal: 
Neuroreport
PubMed ID: 
20848732
Pagination: 
452-6
Volume: 
21
Issue: 
6
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.
Published Date: 
April, 2010

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