The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice

Geoffrey J. Markowitz, Shilpa D. Kadam, Dawn M. Boothe, Natasha D. Irving, Anne M. Comi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)452-456
Number of pages5
JournalNeuroreport
Volume21
Issue number6
DOIs
StatePublished - 2010

Keywords

  • Antiepileptic drugs
  • Brain-to-blood ratios
  • Immature mice
  • Pharmacokinetics
  • Plasma levels

ASJC Scopus subject areas

  • Neuroscience(all)

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