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Plasma levels of methsuximide and N-desmethylmethsuximide during methsuximide therapy

Clinical Pharmacology Laboratory. Division of Medicine, Northwestern Memorial Hospital, the Departments ot Medicine and Pharmacology, Northwestern University Medical School, the Gibbs Laboratories, and the Department of Neurology. Abraham Lincoln School of Medicine, University of Illinois, Chicago.

The plasma concentration of N-desmethylmethsuximide in patients receiving chronic methsuximide therapy averages about 700 times the concentration of the parent drug. Both compounds were measured simultaneously by quadrupole mass fragmentography in the plasma of 17 patients receiving methsuximide for various types of epilepsy. Because methsuximide is only slightly more effective than N-desmethylmethsuximide in anticonvulsant tests on laboratory animals, it is likely that Ndesmethylmethsuximide is primarily responsible for seizure control in these patients. Although more study is needed to define the precise range of therapeutically effective plasma concentrations, plasma levels of N-desmethylmethsuximide below 10 mcg per milliliter appear to be ineffective while those above 40 mcg per milliliter are toxic.

Dr. Atkinson's address is Clinical Pharmacology Laboratory, Passavant Pavilion, Northwestern Memorial Hospital, 303 E. Superior Street, Chicago 60611

Dr. Strong is a postdoctnral fellow in pharmacology, supported by the National Institute ot General Medical Sciences. NIH grant No. (GM-52 667), Dr. Atkinson is a Burroughs Wellcome Scholar in Clinical Pharmacology. This work was partly supported by research funds of the Gibbs Laburatories.

Received for publication August 23, 1973.

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