Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs

K. Orito, M. Saito, K. Fukunaga, E. Matsuo, S. Takikawa, M. Muto, K. Mishima, N. Egashira, M. Fujiwara

研究成果: ジャーナルへの寄稿学術誌査読

30 被引用数 (Scopus)

抄録

The purposes of the present study were to elucidate the pharmacokinetics of zonisamide, determine the presence of a drug interaction with phenobarbital, and evaluate how long any interaction lasted after discontinuation of phenobarbital in dogs. Five dogs received zonisamide (5 mg/kg, p.o. and i.v.) before and during repeated oral administration of phenobarbital (5 mg/kg, bid, for 30-35 days). Zonisamide (5 mg/kg, p.o.) was also administered 8, 10, and 12 weeks after discontinuation of phenobarbital. Blood was sampled until 24 h after each zonisamide administration and serum concentrations of zonisamide were determined. Repeated phenobarbital decreased the maximum serum concentration, area under the serum concentration vs. time curve, apparent elimination half-life, and bioavailability of zonisamide. Total clearance increased. Time to maximum serum concentration and volume distribution were not changed. The maximum serum concentration and area under the serum concentration vs. time curve of zonisamide continued to be low until 10 weeks after the discontinuation of phenobarbital. They were restored to the same serum concentration as before phenobarbital administration 12 weeks after the discontinuation of phenobarbital. These data suggested that repeated administration of a clinical dose of phenobarbital enhanced the clearance of zonisamide and the enhanced clearance lasted at least 10 weeks after the discontinuation of phenobarbital. Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide.

本文言語英語
ページ(範囲)259-264
ページ数6
ジャーナルJournal of Veterinary Pharmacology and Therapeutics
31
3
DOI
出版ステータス出版済み - 6月 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 獣医学(全般)

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