Cross-Reactivity of Fosphenytoin in Four Phenytoin Immunoassays

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Abstract
Fosphenytoin, 5,5-diphenyl-3-[(phosphonooxy)methyl]-2,4-imidazolidine-dione disodium salt (Cerebyx®; ParkeDavis), is a phosphorylated form of the anticonvulsant drug phenytoin. Fosphenytoin itself has no pharmacological activity but is dephosphorylated in vivo by phosphorylases to the active drug, phenytoin. The elimination half-life of fosphenytoin in plasma is 8–15 min in healthy subjects ( 1)( 2). Fosphenytoin can be used for parenteral or intramuscular administration, where its superior aqueous solubility results in less severe side effects than does phenytoin ( 2)( 3). Few data, however, are available on the interference of fosphenytoin in phenytoin immunoassays, which are currently the most common method used to monitor patients’ phenytoin concentrations. In an abstract ( 4), Kugler et al. reported that the TDx® Phenytoin assay (Abbott Labs.) was interfered with by fosphenytoin. We report here the results of detailed cross-reactivity studies for fosphenytoin in four phenytoin im-munoassays: ACS:180® Automated Chemiluminescence System (Chiron Diagnostics), TDx Phenytoin and Phenytoin II, and AxSym® Phenytoin II (also from Abbott Labs.).