Concentrations of Idoxuridine in Serum, Urine, and Cerebrospinal Fluid of Patients with Suspected Diagnoses of Herpesvirus hominis Encephalitis

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Abstract
A reproducible microbiologic assay of microgram quantities of idoxuridine (IDU) in serum, urine, or cerebrospinal fluid is presented. The antiviral assay is not interfered with by type-specific antibody or interferon. During slow intravenous infusions of idox-uridine (4 mg/min) in patients with suspected diagnoses of Herpesvirus hominis encephalitis, the rate of inactivation and/or removal of drug exceeded its administration. During several rapid infusions of idoxuridine (50 mg/min) significant quantities of the drug were found in serum, urine, and cerebrospinal fluid. Idoxuridine is not significantly bound to serum proteins and is not deiodinated in fresh serum or urine in vitro to inactive products (iodouracil, uracil, iodide). It is rapidly excreted into the urine. Inactivation of IDU occurs in tissues. This antiviral assay of IDU in body fluids should be applicable to other viruses and potential antiviral agents. Minimal inhibitory concentrations of IDU for fresh isolates of Herpesvirus hominis (type 1 or 2) were determined. Type 1 herpesviruses' microplaques in baby hamster kidney cell (BHK 21) tissue cultures were sensitive to 2.5-10 μg/0.4 ml. Type 2 macroplaques required 25-50 μg/0.4 ml. This latter characteristic may be an additional biologic marker which may be useful in suggesting type-specificity of herpesvirus isolates.