Methsuximide for complex partial seizures: efficacy, toxicity, clinical pharmacology, and drug interactions.
Methsuximide (MSM; Celontin) was administered for 8 weeks to 26 patients with complex partial seizures (CPS) refractory to phenytoin and carbamazepine and phenobarbital or primidone. A 50% or greater reduction in CPS frequency was obtained in eight patients. MSM therapy was continued chronically in these eight patients, and five continued to have a 50% or greater reduction in CPS frequency after 3 to 34 months of follow-up. Drowsiness, gastrointestinal disturbance, hiccups, irritability, and headache were the common side effects of MSM. No serious toxicity occurred. N-desmethylmethsuximide was the principal substance detected in plasma and had the following pharmacokinetic values: accumulation half-life, 49.7 hours; time to steady state, 10.4 days; elimination half-life, 72.2 hours; therapeutic range of plasma concentration, 10 to 30 mg per liter. Plasma concentrations of phenytoin and phenobarbital derived from primidone rose significantly (p less than 0.05) after addition of MSM.
D000328:Adult; D001702:Biopharmaceutics; D001921:Brain / Q000503:physiopathology; D004347:Drug Interactions; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006606:Hiccup / Q000139:chemically induced; D006801:Humans; D012894:Sleep Stages; D013388:Succinimides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D013388:Succinimides; C100286:methsuximide