Dietary iron reduces the anti-convulsion activity of phenytoin in electroconvulsion via inhibition of brain penetration.
We determined the anti-convulsion activity of phenytoin (PHT) using the maximum electron shock method in mice fed diets containing various concentrations of iron for 18 weeks. Dietary iron reduces the anti-convulsion activity of PHT in a dose-dependent manner (0-6100 ppm). High concentrations of PHT are detected in the plasma of mice fed a high iron diet compared with those fed normal and low iron diets, in contrast to the pharmacological effect. However, the concentration of PHT in the brains of mice fed high amounts of dietary iron decreased significantly 3 h after treatment with PHT, consistent with the anti-convulsion effect of PHT. The relationship between brain and plasma-unbound concentrations of PHT indicates that the penetration of PHT into brain is significantly inhibited by dietary iron.
Mizukami
Y
Y
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. mizukami@po.cc.yamaguchi-u.ac.jp
Yamada
S
S
Kokudo
N
N
Takashima
M
M
Yokoyama
T
T
D000818:Animals; D000927:Anticonvulsants / Q000097:blood*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004597:Electroshock; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D005526:Food, Formulated / Q000009:adverse effects*; D006400:Hematocrit; D007501:Iron / Q000097:blood*; D000090463:Iron Deficiencies; D008297:Male; D051379:Mice; D010672:Phenytoin / Q000097:blood*
D000927:Anticonvulsants; D010672:Phenytoin; D007501:Iron