1. A once-per-day, drug-in-food protocol for prolonged administration of antiepileptic drugs in animal models.
- Author
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Ali A, Dua Y, Constance JE, Franklin MR, and Dudek FE
- Subjects
- Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Epilepsy, Food, Formulated, Kainic Acid, Male, Pharmaceutical Preparations administration & dosage, Rats, Time Factors, Treatment Outcome, Anticonvulsants administration & dosage, Anticonvulsants pharmacology, Carbamazepine administration & dosage, Carbamazepine pharmacology, Seizures drug therapy, Status Epilepticus drug therapy
- Abstract
Purpose: Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof-of-principle study aimed to optimize a once-per-day, drug-in-food protocol by testing the effect of carbamazepine (CBZ) on the frequency of convulsive seizures in rats with kainate-induced epilepsy., Methods: Adult male rats were given repeated low-dose kainate injections until convulsive status epilepticus persisted for >3 h. After the rats developed spontaneous recurrent seizures, food pellets with CBZ (30, 100, or 300 mg/kg/day) were provided once per day in three 2-week trials (n = 7-9 rats) involving 5 days of CBZ or control treatment, separated by two recovery days within a trial. The total amount of food provided and consumed per day corresponded to a normal caloric diet (60 g/kg/day)., Key Findings: When provided once per day, all animals ate the CBZ-containing food irregularly but continuously throughout the 24-h day. With this daily feeding protocol, CBZ significantly reduced the frequency of spontaneous convulsive seizures in a dose-dependent manner. It is important to note that the effect of CBZ was consistent across the 5 days and throughout each day of the trials. With food administered at 9:00 a.m., and blood assayed at 5:00 p.m., higher food levels of CBZ resulted in higher plasma concentrations of CBZ., Significance: This AED-in-food protocol is simple, efficient, inexpensive, reliable, and noninvasive; it allows easier long-term drug administration and is less stressful and more humane than other methods of AED administration., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)
- Published
- 2012
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