Chronic primidone treatment in the rat: an animal model of primidone therapy.

A continuously protective, nontoxic, oral model of chronic treatment with primidone was developed in the rat. Rats were treated with primidone (100 mg/kg) by gastric gavage twice daily for up to 8 weeks. This treatment was continuously protective as measured by seizures induced by hexafluorodiethyl ether and minimally toxic as measured by weight gain. Plasma primidone concentration reached a peak (13 micrograms/ml) 2 hours after gavage and was almost undetectable by 12 hours. Plasma phenobarbital concentration peaked (52 micrograms/ml) at 6 hours postgavage after reaching a minimum (19 micrograms/ml) at one hour postgavage. Phenobarbital concentrations measured in plasma, brain and liver after 8 weeks of chronic treatment correlated significantly between each tissue and plasma.