Pharmacokinetic study of trimethadione and its metabolite in blood, liver and brain by microdialysis in conscious, unrestrained rats.
A microdialysis method has been developed in the past two decades to determine levels of drug and endogenous compounds in several organs under physiological conditions. In this study, we determined the pharmacokinetics of the model drug, trimethadione (TMO), and its only metabolite, dimethadione (DMO), in liver, blood and brain by the microdialysis method in freely-moving rats. Sampling times were extended up to 24 hours. The construction of a newly developed microdialysis probe for liver and blood is described. The elimination patterns of TMO in liver, blood and brain dialyzates were almost identical and the calculated t1/2 was approximately 3 hr in each sample. However, in brain, tmax was delayed compared with the others while the relative concentration of DMO (AUC0-24h) was lower in brain compared with liver and blood. These studies suggest that this concurrent and successive microdialysis sampling method will not only be a useful tool for pharmacokinetic and drug metabolism studies in the organs of small animals but will also decrease the number of experimental animals needed for a study.
Kurata
N
N
Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
Inagaki
M
M
Iwase
M
M
Nishimura
Y
Y
Kiuchi
Y
Y
Yamazaki
Y
Y
Kobayashi
S
S
Oguchi
K
K
Uchida
E
E
Yasuhara
H
H
D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004114:Dimethadione / Q000493:pharmacokinetics*; D005625:Frontal Lobe / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014293:Trimethadione / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D004114:Dimethadione; D014293:Trimethadione