This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koch, S. Articles by Naidech, A. M. Search for Related Content PubMed PubMed Citation Articles by Koch, S. Articles by Naidech, A. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB PHENYTOIN SODIUM

(Stroke. 2005;36:2070.)
© 2005 American Heart Association, Inc.

Letters to the Editor

Phenytoin and Cognitive Decline

Sebastian Koch, MD

Department of Neurology, University of Miami, Miami, Fla

Barry E. Gidal, PharmD

School of Pharmacy and Department of Neurology, University of Wisconsin, Madison, Wisc

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

We read with great interest the article by Naidech et al¹ on the association of phenytoin exposure and cognitive disability after subarachnoid hemorrhage. The authors speculate on a number of reasons for this association, to which we would like to add the possibility of a pharmacokinetic interaction compromising the protective effects of nimodipine.

Phenytoin induces the hepatic microsomal enzyme system (cytochrome p-450 isozymes). Induction of the CYP isozyme system may begin within 48 hours of phenytoin administration.² Nimodipine is a high extraction ratio drug and undergoes extensive first-pass metabolism in both the intestinal wall and liver. The oral bioavailability of nimodipine is less than 13%. The metabolism of nimodipine is mediated primarily by cytochrome p-450 (CYP 3A4). Indeed, it is reasonable to speculate that a pharmacokinetic interaction may exist between these 2 agents that may result in reduced efficacy of nimodipine.

A study evaluating nimodipine pharmacokinetics in a group of epileptic patients found that comedication with the CYP inducers phenytoin or carbamazepine resulted in a decrease of the area under the concentration time curve (AUC) of nimodipine of approximately 85%.³ In other words, treatment with an inducing antiepileptic drug such as phenytoin significantly reduces nimodipine bioavailability. In this same trial, patients receiving concomitant valproic acid (an antiepileptic drug that does not induce CYP 3A4) did not result in a reduction in nimodipine AUC. The clinical implications of this are that nimodipine oral doses may need to be substantially increased to compensate for this reduced bioavailability.

Vasospasm and . . . [Full Text of this Article]

Andrew M. Naidech, MD, MSPH

Northwestern University Medical School, Chicago, Ill

This article has been cited by other articles:

				G. K.C. Wong, W. S. Poon, and A. M. Naidech Use of Phenytoin and Other Anticonvulsant Prophylaxis in Patients With Aneurysmal Subarachnoid Hemorrhage * Response: Stroke, December 1, 2005; 36(12): 2532 - 2532. [Full Text] [PDF]