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Phenytoin pharmacokinetics in catamenial epilepsy

From the Department of Physiology and Pharmacology (Mr. Shavit and Drs. Korczyn and Gitter), Sackler School of Medicine, Tel Aviv University, Ramat Aviv; the Pediatric Seizure Clinic (Drs. Lerman and Kivity) and the Department of Neurology (Dr. Bechar), Beilinson Hospital, Petah Tikva; and the Department of Neurology (Dr. Korczyn), Ichilov Hospital, Tel Aviv, Israel.

It is not known why the frequency of seizures sometimes increases in the perimenstrual period (catamenial epilepsy). We have examined the possibility that changes in anticonvulsant pharmacokinetics may be responsible. Seventeen women with seizures who were taking\ phenytoin (DPH) and whose seizures were more frequent perimenstrually were examined twice each, once on the first or second menstrual day and again after 2 weeks. Mean serum DPH levels were lower during the menses. In seven women with seizures unrelated to menses, the fall of DPH levels was much smaller. In catamenial epilepsy, the fall was due to increased DPH clearance. At the time of ovulation, hepatic DPH metabolism may be slowed by competition from steroid hormones.

Address correspondence and reprint requests to Dr. Korczyn, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel, 69978.

This work was supported in part by the Andy Lebach Chair for Clinical Pharmacology and Toxicology.

Accepted for publication November 10, 1983.

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