Biotransformation and elimination of [2-(14)C]-1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-5-iodocytosine in immunosuppressed patients with herpesvirus infections Journal Article
| Authors: | Feinberg, A.; Leyland-Jones, B.; Fanucchi, M. P.; Hancock, C.; Fox, J. J.; Watanabe, K. A.; Vidal, P. M.; Williams, L.; Young, C. W.; Philips, F. S. |
| Article Title: | Biotransformation and elimination of [2-(14)C]-1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-5-iodocytosine in immunosuppressed patients with herpesvirus infections |
| Abstract: | The metabolism of the drug [2-14C]-1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-5-iodocytosine (FIAC), a potent inhibitor of herpesvirus replication, was studied in immunosuppressed patients with herpesvirus infections. FIAC was administered intravenously by 15-min infusion and by mouth 24 h later to four patients at doses of 50 or 100 mg/m2. FIAC was cleared from the plasma primarily by biotransformation in liver, kidney, and peripheral blood, with a terminal-phase half-life of 0.92 to 1.80 h (mean, 1.36 h) after intravenous administration. The area under the concentration-time curve from zero to infinity (AUC(0-∞)) for FIAC was 1.6 to 4.7% (mean, 3.4%) of the AUC(0-∞) for total radioactivity. 1-(2'-Deoxy-2'-fluoro-β-D-arabinofuranosyl)-5-iodouracil (FIAU) was the major metabolite; the AUC(0-∞) for FIAU was 54.3 to 72.5% (mean, 63.4%) of the AUC(0-∞) for total radioactivity. The terminal-phase half-life for FIAU was 3.32 to 4.49 h (mean, 3.91 h); FIAU was cleared from plasma by renal elimination and further biotransformation. Lesser amounts of 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)uracil, 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)cytosine, the glucuronide conjugates of these metabolites, and the glucuronide conjugates of FIAC and FIAU were also formed. A comparison of the AUC(0-∞) for total radioactivity after intravenous and oral administration suggested that nearly all of the oral dose was absorbed. Plasma levels of FIAU, also a potent inhibitor of herpesvirus replication in vitro, exceeded the 50% effective dose for herpes simplex virus and varicella-zoster virus as late as 12 h after administration of FIAC. |
| Keywords: | clinical article; controlled study; unclassified drug; dose response; drug response; herpes virus; drug clearance; fialuridine; drug metabolism; drug blood level; radioisotope; drug half life; immunosuppressive treatment; herpes simplex virus; therapy; intravenous drug administration; pharmacokinetics; drug urine level; oral drug administration; drug elimination; drug identification; varicella zoster virus; fiacitabine; human; priority journal; article; drug analysis; 2' fluoro 5 iodocytarabine c 14; 2' fluoro 2' deoxycytosine arabinoside; 2' fluoro 2' deoxyuracil arabinoside |
| Journal Title: | Antimicrobial Agents and Chemotherapy |
| Volume: | 27 |
| Issue: | 5 |
| ISSN: | 0066-4804 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1985-05-01 |
| Start Page: | 733 |
| End Page: | 738 |
| Language: | English |
| DOI: | 10.1128/aac.27.5.733 |
| PROVIDER: | scopus |
| PMCID: | PMC180143 |
| PUBMED: | 2990323 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work