Subject(s)
Humans , Clinical Protocols/standards , Epilepsy/diagnosis , Epilepsy/drug therapy , Phenobarbital/administration & dosage , Phenytoin/administration & dosage , Primidone/administration & dosage , Carbamazepine/administration & dosage , Valproic Acid/administration & dosage , Receptors, GABA-A/administration & dosage , Vigabatrin/administration & dosage , Ethosuximide/administration & dosageABSTRACT
Male Wistar rats were subjected to daily sessions of electrical amygdala kindling until a generalized seizure was observed on five consecutive days. Bilateral microinjections (0.5 microliter) of ethosuximide (ETX) (10 pg/microliters) or saline were then administered through guide cannulas into the substantia nigra (pars reticulata). No significant difference was observed between the ETX (N = 8) and saline (N = 8) groups in duration of afterdischarge or in the latency for stage 5 generalized seizures. Our results indicate that ETX applied to the substantia nigra is not effective in suppressing amygdala-kindled seizures.
Subject(s)
Amygdala/drug effects , Ethosuximide/pharmacology , Kindling, Neurologic/drug effects , Seizures/prevention & control , Substantia Nigra/physiology , Amygdala/physiology , Animals , Electric Stimulation , Electroencephalography , Ethosuximide/administration & dosage , Kindling, Neurologic/physiology , Male , Microinjections , Rats , Rats, Inbred Strains , Substantia Nigra/drug effectsABSTRACT
Male Wistar rats were sugjected to daily sessions of electrical amygdala kindling until a generalized seixure was observed on five consecutive days. Bilateral microinections (0.5 micronl) of ethosuximide (ETX) (10 pg/micronl) or saline were then administered though guide cannulas into the substantia nigra (pars reticulata). No significant difference was observed between the ETX (N = 8) and saline (N = 8) groups in duration of afterdischarge or in the latency for stage 5 generalized seizures. Our results indicate that ETX applied to the substantia nigra is not effective in suppressing amydala-kindled seizure
Subject(s)
Rats , Animals , Male , Amygdala/drug effects , Ethosuximide/pharmacology , Kindling, Neurologic/drug effects , Seizures/physiopathology , Substantia Nigra/physiology , Amygdala/physiology , Electric Stimulation , Electroencephalography , Ethosuximide/administration & dosage , Kindling, Neurologic/physiology , Microinjections , Rats, Inbred Strains , Substantia NigraABSTRACT
Carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-epox) steady-state serum concentrations were measured in 82 children who had generalized tonic-clonic, or partial seizures. There was no correlation between a given dose and serum concentrations, whether other anticonvulsant drugs were used or not. Epileptic children receiving polytherapy (CBZ associated with one or more of the following drugs: phenobarbital, primidone, phenytoin, ethosuximide) had significantly different CBZ clearance values and percent CBZ-epox than did patients given CBZ alone. Even though given lower doses, girls had higher CBZ concentrations and lower CBZ clearance values than did boys. Older girls had lower serum concentrations of CBZ-epox than did younger girls. Seizure-free children had higher CBZ serum levels and lower CBZ clearance values than did those with uncontrolled seizures. The percentage of CBZ-epox in children with uncontrolled seizures was significantly higher than in children without seizures. These data indicate that serum levels of CBZ and CBZ-epox correlate more with factors such as associated drugs, age, and sex than with administered dose. Therefore, CBZ serum level monitoring represents an essential means of individualization of anticonvulsant drug therapy.
Subject(s)
Carbamazepine/analogs & derivatives , Carbamazepine/administration & dosage , Epilepsy/drug therapy , Adolescent , Age Factors , Carbamazepine/blood , Carbamazepine/metabolism , Child , Child, Preschool , Drug Therapy, Combination , Epilepsy/blood , Ethosuximide/administration & dosage , Female , Humans , Infant , Kinetics , Male , Phenobarbital/administration & dosage , Phenytoin/administration & dosage , Primidone/administration & dosage , Sex FactorsABSTRACT
In two children treated for hypoglycemia and convulsions with diazoxide and diphenylhydantoin, therapeutic serum diphenylhydantoin levels were not achieved despite doses of diphenylhydantoin of 17 and 29 mg/kg/day, respectively. After diazoxide was discontinued, serum diphenylhydantoin levels were within the therapeutic range in each patient with doses of 6.6 and 10 mg/kg/day, respectively. Serum diphenylhydantoin fell to undetectable levels within four days after experimental reinitiation of diazoxide administration in one patient. Although the mechanism for the effect of diazoxide on serum concentrations of diphenylhydantoin is uncertain, an increased rate of metabolism of diphenylhydantoin is suggested by our findings. Decreased plasma protein binding of diphenylhydantoin, induced by diazoxide, was observed and may play a role.