Chronotoxicity of Sodium Valproate in Pregnant Mouse and Embryo
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概要
- 論文の詳細を見る
The influence of dosing time on the embryotoxicity of sodium valproate (valproic acid, VPA) was investigated in ICR mice under a light-dark (12 : 12) cycle. A significant circadian rhythm was shown for VPA-induced embryotoxicity, with the highest value at 1700 and the lowest at 0100. A similar pattern of rhythm was also shown for VPA-induced toxicity in pregnant and nonpregnant mice. No significant dosing time-dependent difference between injection at 1700 and 0100 was demonstrated for VPA concentrations in the embryo, plasma and brain. The rhythm in the embryotoxicity seems to be related to the rhythm in the sensitivity of the embryo and dam to the drug. Embryotoxicity and VPA concentrations were significantly higher on gestational day 13 than day 7. The pharmacokinetics of VPA contribute, at least partly, to the gestational stage-dependent embryotoxicity of VPA. The timing of drug administration (i.e., gestational stage and circadian phase) appears to be essential for studies on the embryotoxicity of VPA in mice.
- 社団法人 日本薬理学会の論文
- 1996-03-01
著者
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WATANABE Hirokazu
Department of Dermatology, Graduate School of Medicine, University of Toyama
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OHDO Shigehiro
Department of Pharmaceutics, Division of Pharmaceutical Science, Graduate School, Kyushu University
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Ogawa Nobuya
Department Of Pharmacology Ehime University School Of Medicine
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Ogawa Nobuya
Department Of Clinical Pharmacology Ehime University School Of Medicine
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Yoshiyama Y
Division Of Clinical Pharmacy Kyoritsu University Of Pharmacy
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Ohdo Shigehiro
Pharmaceutics Division Of Clinical Pharmacy Department Of Medico-pharmaceutical Science Faculty Of P
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Ohdo Shigehiro
Department Of Pharmaceutics Division Of Pharmaceutical Science Graduate School Kyushu University
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Watanabe Hirokazu
Department Of Biochemistry Faculty Of Pharmaceutical Sciences Kanazawa University:(present Address)
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Ohdo Shigehiro
Department Of Clinical Pharmacokinetics Division Of Pharmaceutical Sciences Kyushu University
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YOSHIYAMA Yuji
School of Pharmaceutical Sciences, Kitasato University
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SUGIYAMA Takashi
School of Pharmaceutical Sciences, Kitasato University
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Watanabe Hirokazu
Department Of Applied Chemistry Nagoya Institute Of Technology
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Sugiyama Takashi
School Of Pharmaceutical Sciences Kitasato University
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OGAWA Nobuya
Department of Pharmacology, Ehime University School of Medicine
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