Chronopharmacokinetics of valproic acid following constant-rate administration in mice

Shigehiro Ohdo, Shigeyuki Nakano, Nobuya Ogawa

研究成果: ジャーナルへの寄稿学術誌査読

28 被引用数 (Scopus)

抄録

This study was carried out to investigate the circadian rhythm in the pharmacokinetics of valproic acid (VPA). ICR male mice, housed under a light-dark (12 h: 12 h) cycle, were used in these studies. In the constant-rate administration study (536.3 or 1,072.6 μg/h), osmotic minipumps were implanted subcutane-ously in mice. There was a significant circadian rhythm in plasma VPA concentrations: higher values were obtained in the light phase and lower values were found during the dark phase. A significant circadian rhythm also was shown for clearance (CL) of the drug: lower values were obtained in the light phase and higher values were demonstrated in the dark phase. In the intravenous administration study, VPA (50 mg/kg) was injected into a tail vein of the mice. Mean plasma VPA concentrations were significantly higher in mice injected with the drug at 1700 h than at 0100 h. The CL was higher, the volume of distribution (V) was larger, and the area under the curve (AUC) was smaller (p < 0.05, respectively) in mice injected with the drug at 0100 h than at 1700 h. As the values of CL and V increased similarly during the dark period, there was no effect on half-life (/1/2) and obviously on the elimination rate constant (K). These findings indicate that the circadian rhythms of plasma VPA concentrations observed after constant-rate administration are due to those of CL and V. To keep drug concentrations constant, the drug release rate from the osmotic minipump should be controlled according to the rhythm of drug pharmacokinetics.

本文言語英語
ページ(範囲)35-43
ページ数9
ジャーナルChronobiology International
8
1
DOI
出版ステータス出版済み - 1991
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 生理学(医学)

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