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June 1987

Volume of Distribution of Phenytoin Not Altered in Storage Disease

Author Affiliations

Departments of Clinical Pharmacology and Pediatrics
Departments of Neurology and Pediatrics
Department of Clinical Chemistry The Hospital for Sick Children 555 University Ave Toronto, Ontario, Canada M5G 1X8

Arch Neurol. 1987;44(6):577-578. doi:10.1001/archneur.1987.00520180003001

To the Editor.  —Anticonvulsant therapy is often required in children with a variety of lysosomal storage disorders. As a part of our therapeutic drug monitoring service, we have been asked to see a number of children with storage disorders in whom therapeutic phenytoin levels were difficult to achieve. Available clinical data have not been adequate to distinguish increased volume of distribution, rapid excretion, or a combination of these factors as an explanation of diminished levels. Although rapid metabolism of phenytoin is common in the pediatric age group,1 one could postulate that lipophilic drugs might have an increased volume of distribution in these patients because of the large amounts of stored lipid material and/ or lysosomal membrane material. A larger volume of distribution would require substantially larger loading doses to achieve a given serum concentration of the drug, although ultimate steady-state concentrations would be unaffected. We have performed a formal pharmacokinetic study

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