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Increased brain uptake of lidocaine during bicuculline-induced status epilepticus in rats

Departments of Neurology (Dr. Simon and Mr. Bronstein) and Medicine (Drs. Benowitz and Jacob), School of Medicine, University of California, San Francisco, and the Neurology Service (Dr. Simon and Mr. Bronstein) and Clinical Pharmacology Unit (Drs. Benowitz and Jacob) of Medical Service, San Francisco General Hospital Medical Center, San Francisco, CA.

Following rapid IV injection (0.1 mg per kilogram) lidocaine HC1 concentrations were measured in the blood and brain of paralyzed, ventilated rats during bicuculline-induced status epilepticus and in identically prepared controls. The concentration of lidocaine in blood and brain was consistently higher in convulsing than in noncon- vulsing rats. At 1 minute, increased brain lidocaine reflected elevated blood concentrations; increased brain and blood partitioning after 1 minute is responsible for subsequent increases in brain lidocaine uptake. The therapeutic index of lidocaine is low; the concentration of lidocaine is increased in the convulsing brain. Our data suggest that conventional lidocaine doses may perpetuate rather than control refractory convulsions.

Address correspondence and reprint requests to Dr. Simon, Neurology Service, 4M62, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110.

Support is provided in part by Public Health Service Grants DA02453, NS00437, and a University of California, San Francisco Academic Senate Grant 2-503748-34935. Dr. Simon is a recipient of a Teacher Investigator Award #NS00437.

Accepted for publication August 4, 1981.

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