Time course of audiogenic seizure susceptibility and plasma pentobarbital concentration during withdrawal.

Rats were made dependent on sodium barbital by daily oral administration of the drug over a 4 week period. At the end of this time the animals were switched to sodium pentobarbital, I.P., 30 mg/Kg every 4 hours for 3 days and withdrawn. Mean Plasma pentobarbital concentrations was observed to decline rapidly following peak concentrations which occurred approximately 1 hour after the final dose. The last samples in which pentobarbital was detectable were taken 3 hours after the last dose. Audiogenic seizure susceptibility and intensity peaked at 6 hours following the last dose, suggesting that a low concentration of barbiturate is more important in increasing seizure propensity than a sudden decrease in concentration. No electroencephalographic abnormalities were observed during the withdrawal period.