The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice.
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.
Markowitz
Geoffrey J
GJ
Department of Neurology and Developmental Medicine, Kennedy Krieger Research Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kadam
Shilpa D
SD
Boothe
Dawn M
DM
Irving
Natasha D
ND
Comi
Anne M
AM
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy*; D006207:Half-Life; D007274:Injections, Intraperitoneal / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity
D000927:Anticonvulsants