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Methsuxirnide for complex partial seizures

Efficacy, toxicity, clinical pharmacology, and drug interactions

From the Departments of Neurology, Boston University School of Medicine and Boston Veterans Administration Medical Center (Drs. Browne and Feldman, Ms. Allen, Ms. Fawcett-Vickers, Mr. Szabo, Ms. Mattson, and Ms. Norman), Boston, MA; Clinical Research Department, Warner-Lambert Parke-Davis Company (Dr. Buchanan), Ann Arbor, MI; Departments of Psychiatry and Medicine, Tufts University School of Medicine (Dr. Greenblatt), Boston, MA.

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 < 0.05) after addition of MSM.

Address correspondence and reprint requests to Dr. Browne, Neurology Service (127), Veterans Administration Medical Center, 150 South Huntington Avenue, Boston. MA 02130.

Supported in part by the Clinical Research Department, Warner-Lambert/Parke-Davis Company (all investigators), by the Veterans Administration (Dr. Browne), and by Grant No. NIH-12279 from the US Public Health Service (Dr. Greenblatt).

Portions of this paper were presented at the thirty-second annual meeting of the American Academy of Neurology, New Orleans, LA, April 1980.

Accepted for publication July 1, 1982.

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