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薬理と治療
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Abstract
Objectives To study the tissue distribution and transfer into the fetus or milk of topiramate in rats. Methods [14C]−topiramate was orally administered to male rats, and pregnant and lactating female rats at a dose of 40 mg/kg. Then, blood, tissues, fetus, and milk were collected and analyzed for radioactivity. Results Tissue concentrations of radioactivity in male rats showed the maximum levels in most tissues at 0.5 hours after administration. The concentration in the brain was 40−50% of that in plasma up to 4 hours after administration, while the levels in other tissues were lower than or equal to the level in plasma. Radioactivity levels decreased to 1.4% or lower of the maximum levels in all tissues at 72 hours. After administration to pregnant rats on the 19th day of gestation, radioactivity was transferred into the fetus. The concentration in the fetus was close to that in maternal plasma and decreased in parallel with the maternal plasma level. The concentration in milk reached the maximum level(24.32μg eq./g)1.40 hours after administration to lactating rats on the 9th day after delivery, which levels decreasing faster than what was observed in plasma. The milk/plasma concentration ratio was 0.07−0.73 and decreased with time. Conclusions Topiramate was distributed into most tissues including the brain and transferred to the fetus and milk in rats. However, the elimination rate of concentrations in tissues, fetus and milk was faster than or equal to that in plasma. These data suggested topiramate did not remain in the body over a long period. (Jpn Pharmacol Ther 2008;36:493−9) KEY WORDS Topiramate, Distribution, Pregnancy, Milk, Pharmacokinetics
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