Metabolism of anti-herpes agent 5-(2-chloroethyl)-2'-deoxyuridine in mice and rats

• Published in: European journal of drug metabolism and pharmacokinetics Vol. 16; no. 2; p. 129
• Main Authors: Szinai, I, Veres, Z, Ganzler, K, Hegedus-Vajda, J, De Clercq, E
• Format: Journal Article
• Language: English
• Published: France 01.04.1991
• Subjects: Animals; Antiviral Agents - metabolism; Antiviral Agents - urine; Chromatography, High Pressure Liquid; Circular Dichroism; Deoxyuridine - analogs & derivatives; Deoxyuridine - metabolism; Deoxyuridine - urine; Feces - chemistry; Male; Mass Spectrometry; Mice; Microwaves; Radiometry; Rats; Rats, Inbred Strains; Spectrometry, Mass, Fast Atom Bombardment; Thymidine Phosphorylase - metabolism; Uridine Phosphorylase - metabolism
• ISSN: 0378-7966
• DOI: 10.1007/BF03189949

The enzymatic splitting and metabolic elimination of anti-viral agent 5-(2-chloroethyl)-2'-deoxyuridine [CEDU] have been studied. For elucidation of structures of metabolites, several different kinds of extraction, purification and spectroscopic methods were used (Extrelut LC, TLC, HPLC, MS, NMR, IR, UV and CD). For mass spectral analysis, various ionization techniques (EI, CI and FAB-MS) were performed as complementary methods. After oral administration of [14C]-CEDU to mice and rats, the parent compound, 5-(2chloroethyl) uracil [CEU] and hydroxylated CEU metabolites were isolated and identified from urine and faeces by the above mentioned methods. The CEDU showed rapid phosphorolysis in vitro with thymidine phosphorylase Km 41.0 +/- 5.0; and uridine phosphorylase Km 10.0 +/- 1.5. The cleavage of the N-glycosidic bond of the nucleoside analogue and a new metabolic pathway of CEDU [stereoselective oxidation of 5-(2-chloroethyl) uracil] was observed in both species.