生物活性

• 描述Cidofovir is a synthetic nucleotide analog with potent antiviral activity against a wide range of herpes viruses. Cidofovir dihydrate (1-((S)-3-Hydroxy-2-(phosphonomethoxy)propyl) cytosine dihydrate) is the active intracellular metabolite of cidofovir that can inhibit cytomegalovirus DNA polymerase^[1]. In A549 cells, the analysis of 50% inhibitory dose (ID₅₀) of cidofovir dihydrate in different strains and serotypes of adenovirus showed that the mean ID₅₀ values for Ad5 wide-type, Ad5 McEwen, Ad14 and Ad8 are 9.5, 7.3, 5.4, and 4.7 μg/mL, respectively^[2]. In MRC-5 cells, the ED₅₀ values of cidofovir dihydrate against H^mc wild type, SC16, BW-S, BW-R, MS wild type are 6.5 ± 2.5, 9.3 ± 1.8, 8.5 ± 1.0, 1.1 ± 0.9, and 9.1 ± 1.8 μM, respectively^[3].. A graded decrease in the severity of acute conjunctivitis was observed in rabbits received the treatment of 0.1% cidofovir dihydrate, whereas the concentrations at 0.5% and 1% caused a moderate grade of acute conjunctivitis. A significantly reduction in Ad5 ocular titers was shown in 0.5% and 1% cidofovir dihydrate-treated groups compared to the placebo group. The duration of viral ocular shedding in 0.1%, 0.5%, and 1% cidofovir dihydrate-treated groups were 6, 4, and 4 days, compared to 7-day duration in placebo group. The mean ELISA antibody titer was decreased by 0.5% and 1% cidofovir dihydrate 21 days post the inoculation^[2].
• 作用机制Cidofovir dihydrate is the active form of cidofovir and it inhibits viral DNA polymerases as an acyclic nucleoside phosphonate^[2].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00019240	Sarcoma	Phase 2	Completed	-	United States, Maryland ... more >> Medicine Branch Bethesda, Maryland, United States, 20892 Collapse <<
  NCT00002437	Cytomegalovirus Retinitis ... more >> HIV Infections Collapse <<	Phase 2	Completed	-	United States, California ... more >> Los Angeles County - USC Med Ctr Los Angeles, California, United States, 90033 UCI Med Ctr Orange, California, United States, 92668 Mount Zion Med Ctr San Francisco, California, United States, 94115 United States, Massachusetts Beth Israel Hosp Boston, Massachusetts, United States, 02215 United States, New Jersey Besselaar Associates Princeton, New Jersey, United States, 085406681 United States, New York Univ of Rochester Med Ctr Rochester, New York, United States, 14607 United States, North Carolina Univ of North Carolina Hosps Chapel Hill, North Carolina, United States, 27599 United States, Texas Audie L Murphy Veterans Administration Hosp San Antonio, Texas, United States, 78284 United Kingdom Charing Cross and Westminster Med School London SW 10, United Kingdom Collapse <<
  NCT00002327	HIV Infections ... more >> Condyloma Acuminata Collapse <<	Phase 1	Completed	-	United States, California ... more >> East Bay AIDS Ctr Berkeley, California, United States, 94705 Univ California San Francisco San Francisco, California, United States, 941430316 United States, Colorado City and County of Denver / Dept of Health & Hosps Denver, Colorado, United States, 802044507 United States, New York Bronx-Lebanon Hosp Ctr Bronx, New York, United States, 10453 Univ of Rochester Med Ctr Rochester, New York, United States, 14642 United States, Texas Houston Clinical Research Network Houston, Texas, United States, 77006 Dr Brad Bowden Houston, Texas, United States, 77027 Dr Stephen Tyring Nassau Bay, Texas, United States, 77058 United States, Utah Univ of Utah School of Medicine Salt Lake City, Utah, United States, 84132 United States, Washington Univ of Washington / Viral Disease Clinic Seattle, Washington, United States, 98122 Pacific Med Ctr Seattle, Washington, United States, 98144 Collapse <<

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• 参考文献

• [1] Davis JL, Taskintuna I, et al. Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis. Arch Ophthalmol. 1997;115(6):733-7.

  [2] de Oliveira CB, Stevenson D, et al. Evaluation of Cidofovir (HPMPC, GS-504) against adenovirus type 5 infection in vitro and in a New Zealand rabbit ocular model. Antiviral Res. 1996;31(3):165-72.

  [3] Mendel DB, Barkhimer DB, et al. Biochemical basis for increased susceptibility to Cidofovir of herpes simplex viruses with altered or deficient thymidine kinase activity. Antimicrob Agents Chemother. 1995;39(9):2120-2.