Biotransformation of 5-(2-chloroethyl)-2'-deoxyuridine in male NMRI mice.
When the selective anti-herpes agent [2-14C]-5-(2-chloroethyl)-2'-deoxyuridine [( 14C]CEDU) was administered as a single oral dose to mice, 87.9% of the radioactivity was excreted in the urine and 11.2% in the feces within 72 hr. Compounds accounting for 84% of the 14C radioactivity in the 0- to 24-hr urine were isolated by various chromatographic techniques and identified by MS, NMR, IR, and CD analysis. Approximately 25% of the radioactivity found in the urine was the parent compound (CEDU). According to the 14C-metabolites detected in the urine, one may infer that [14C]CEDU is metabolized, first, by cleavage of its N-glycosidic bond, resulting in the formation of 5-(2-chloroethyl)uracil (38.7%) and, second, by stereoselective hydroxylation of the alpha carbon atom of the haloalkyl side chain of 5-(2-chloroethyl)uracil, resulting in the formation of 5-(1-hydroxy-2-chloroethyl)uracil (29.6%). CEDU was absorbed rapidly from the gastrointestinal tract and the bloodstream, and did not show any particular accumulation in mouse tissues, as revealed by whole body autoradiography.
Szinai
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Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
de Clercq
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E
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002942:Circular Dichroism; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D005243:Feces / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
C047370:5-(2-chloroethyl)-2'-deoxyuridine; D003857:Deoxyuridine