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The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice.
|Title||The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Markowitz GJ, Kadam SD, Boothe DM, Irving ND, Comi AM|
|Date Published||2010 Apr 21|
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.