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The pyrimidine nucleoside 3'-deoxy-3'fluorothymidine (FLT) inhibits the replication of feline onco- and lenti-retroviruses in vitro and in vivo.

Hardy WD, Zuckerman EE, Boecker J, Corbishley J, Kong XB, Wantanabe KA, Polsky BW, Gold JW, Baron P, Chou TC; International Conference on AIDS.

Int Conf AIDS. 1990 Jun 20-23; 6: 183 (abstract no. Th.A.255).

Memorial Sloan Kettering Cancer Center, NY, NY, USA

OBJECTIVE: To evaluate the ability of FLT to inhibit the replication of feline onco- and lenti-retroviruses, the feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV), in vitro and in vivo. METHODS: The inhibitory effects of FLT were evaluated in vitro by the FeLV and FIV fluorescent focus reduction assays. The EC50 (50% antiviral effective concentrations) of FLT was compared to that of AZT in vitro. Two FeLV-viremic healthy cats were treated orally for 8 weeks with FLT at 30 mg/kg per day. RESULTS: FLT was found to inhibit both FeLV and FIV in vitro. The EC50's against FeLV for FLT and AZT are 1.33 uM and 0.11 uM respectively whereas the EC50's against FIV are 0.07 uM and 0.83 uM respectively. One cat was given a single dose of 2 mg/kg of FLT orally to determine the FLT plasma concentrations obtained and the clearance of the compound. This dose yielded a plasma concentration of 42 uM by 2 hours and the plasma half-life (T 1/2) was 195 minutes. Two healthy chronically FeLV-viremic cats that received FLT showed a 10% reduction of the FeLV antigen positive leukocytes in the peripheral blood by 4 to 6 weeks. Quantitative capture ELISAs for FeLV p27 antigen showed a 3 fold reduction of p27 antigenemia by 6 weeks. Severe myelosuppression (anemia and leukopenia) was noted in both cats by 4 weeks. CONCLUSION: FLT inhibits both onco- and lenti-retroviruses of cats and is able to reduce the FeLV replication in chronically infected pet cats. FLT inhibits the replication of HIV in vitro and should be studied in humans.

Publication Types:
  • Meeting Abstracts
Keywords:
  • Animals
  • Cats
  • Enzyme-Linked Immunosorbent Assay
  • Felidae
  • Felis
  • Humans
  • Immunodeficiency Virus, Feline
  • In Vitro
  • Leukemia Virus, Feline
  • Pyrimidine Nucleosides
  • Retroviridae
  • Retroviridae Infections
  • Zalcitabine
  • Zidovudine
Other ID:
  • 10025590
UI: 102181808

From Meeting Abstracts




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