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.
Carl
G F
GF
Medical Research Service, Veterans Administration Medical Center, Augusta, Georgia 30910.
Smith
M L
ML
D000284:Administration, Oral; D000818:Animals; D008297:Male; D008954:Models, Biological; D010634:Phenobarbital / Q000493:pharmacokinetics; D011324:Primidone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000517:prevention & control; D013997:Time Factors; D014018:Tissue Distribution
D011324:Primidone; D010634:Phenobarbital