THE FATE OF 5-IODO-2'-DEOXYURIDINE (IUdR) IN PLASMA AND CEREBROSPINAL FLUID OF DOGS

¹ Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida

The distribution and metabolism of 5-iodo-2'-deoxyuridine (IUdR) were studied in the cerebrospinal fluid (CSF) and plasma of dogs after i.v. and intracisternal injection. IUdR and iodouracil (IU) were isolated by thin layer chromatography, and inorganic iodide (I) was separated with methyl mercuric bromide and toluene. After i.v. administration of IUdR-I¹²⁵ and IUdR-6H³, CSF/plasma radioactivity ratios were 0.1 and 1, respectively. Analysis of serial plasma samples showed rapid degradation of the drug, with I being responsible for 80% of plasma radioactivity. CSF radioactivity after i.v. injection was almost entirely due to I, indicating that no significant quantities of IUdR reach CSF after i.v. injection. After simultaneous intracisternal injection of IUdR-I¹²⁵, IUdR-6H³ and inulin-C¹⁴ (used as a control substance), radioactivity due to H³ disappeared at the same rate as that due to C¹⁴, whereas I¹²⁵ radioactivity disappeared twice as fast. Analysis of serial CSF samples showed rapid disappearance of IUdR, with concomitant appearance of IU and I. There was no breakdown of IUdR when it was incubated in CSF in vitro. The data suggest that IUdR is rapidly metabolized when injected i.v. or into brain ventricles, probably according to the following scheme: IUdR IU + U. This rapid metabolism may explain the relative ineffectiveness of IUdR when used to treat brain viral infections, even when the drug is given directly into the CSF.