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

I. Szlnai, Z. Veres, K. Ganzler, J. Hegedus-Vajda, E. De Clercq

Research output: Contribution to journalArticle

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Abstract

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 [1 4C]-CEDU to mice and rats, the parent compound, 5-(2chloroethyl) uracil [CEU] and hydroxylated CELT 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 10.0 ± 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.

Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume16
Issue number2
DOIs
Publication statusPublished - Apr 1991

Fingerprint

Deoxyuridine
Uracil
Uridine Phosphorylase
Thymidine Phosphorylase
Metabolic Networks and Pathways
Nucleosides
Feces
Oral Administration
High Pressure Liquid Chromatography
Urine
5-(2-chloroethyl)-2'-deoxyuridine

Keywords

  • 5-(2-chloroethyl)-2′-deoxyuridine
  • metabolism
  • microwave extraction
  • product stereo-selective hydroxylation
  • pyrirnidine nucleoside phosphorylases

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Metabolism of anti-herpes agent 5-(2-chloroethyl)-2′-deoxyuridine in mice and rats. / Szlnai, I.; Veres, Z.; Ganzler, K.; Hegedus-Vajda, J.; De Clercq, E.

In: European Journal of Drug Metabolism and Pharmacokinetics, Vol. 16, No. 2, 04.1991, p. 129-136.

Research output: Contribution to journalArticle

Szlnai, I. ; Veres, Z. ; Ganzler, K. ; Hegedus-Vajda, J. ; De Clercq, E. / Metabolism of anti-herpes agent 5-(2-chloroethyl)-2′-deoxyuridine in mice and rats. In: European Journal of Drug Metabolism and Pharmacokinetics. 1991 ; Vol. 16, No. 2. pp. 129-136.
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