Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs

Journal of Veterinary Pharmacology and Therapeutics - Tập 31 Số 3 - Trang 259-264 - 2008
Kensuke Orito1, Miyoko Saito2, Koya Fukunaga1, Eisuke Matsuo2, Shuichi Takikawa2, Makoto Muto2, Kenichi Mishima3, Nami Egashira3, Michihiro Fujiwara3
1Department of Pharmacology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan
2Department of Surgery II, School of Veterinary Medicine, Azabu University, Kanagawa, Japan
3Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

Tóm tắt

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.

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Thông tin xuất bản

Journal of Veterinary Pharmacology and Therapeutics

Tập 31 Số 3

259-264

Thông tin tác giả