Zonisamide blocks voltage-dependent sodium and calcium channels, enhances actions of GABA and may reduce presynaptic glutamate release (Mac Donald 2002). Furthermore an increase in dopamine and serotonin levels in striatal and hippocampal structures are reported (Kaneko and others 1993, Okada and others 1995). It is metabolised primarily by hepatic microsomal enzymes, and the half-life in dogs is about 15 hours (Matsumoto and others 1983, Thomas 2003). Consequently, the elimination half-life is dramatically shorter in dogs already receiving drugs that stimulate hepatic microsomal enzymes than in dogs who are not receiving such drugs.
Adjunct therapy for canine seizures refractory to standard medication.
An initial dose rate of 10 mg/kg BID is recommended if used as an add-on of drugs requiring hepatic metabolism (e.g., phenobarbital) – Lower dose of 5 mg/kg BID can be used in dogs not concurrently receiving drugs that induce hepatic microsomal enzymes. Trough serum zonisamide concentration should be checked after around 1 week of zonisamide treatment aiming for a serum concentration of 10-40 ug/ml.
Zonisamide appears to be safe - few side-effects are reported in dogs, although mild ataxia and sedation may occur when treatment is started and vomiting and loss of appetite have been reported in some dogs (Dewey and others, 2004).
Has caused kidney stones in some people.
At a dose of 75 mg/kg bodyweight (four times the recommended dose) slight changes in blood count and an increase of liver weight were observed in one study (Walker and others 1988).
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