The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice

Neuroreport. 2010 Apr 21;21(6):452-6. doi: 10.1097/wnr.0b013e328338ba18.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticonvulsants / blood
  • Anticonvulsants / pharmacokinetics*
  • Brain / drug effects*
  • Brain / growth & development
  • Brain / metabolism
  • Disease Models, Animal
  • Epilepsy / drug therapy*
  • Half-Life
  • Injections, Intraperitoneal / methods
  • Mice
  • Mice, Inbred Strains
  • Species Specificity

Substances

  • Anticonvulsants