Experimental thymidine kinase-deficient HSV-1 keratitis: therapeutic attempts.
Trifluridine (TFT) and a structurally related analogue, 5-fluoro-2'-deoxyuridine (FDU), were investigated for their efficacy in the topical treatment of experimental keratitis caused by thymidine kinase-positive (TK+) and thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. Bromovinyldeoxyuridine (BVDU) was used as a reference compound. Both 0.2% BVDU and 0.2% TFT eyedrops produced a highly significant healing of TK+HSV-1 keratitis as compared to the placebo and 0.2% FDU eyedrops (P much less than 0.005), whereas the latter compound did not differ from placebo eyedrops. In the treatment of TK HSV-1 keratitis, none of the drugs exhibited a beneficial healing effect, although the virus strain used was inhibited in vitro by TFT and FDU at a very low concentration (0.02-0.04 microgram/mL).
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005467:Floxuridine / Q000627:therapeutic use*; D007635:Keratitis, Dendritic / Q000188:drug therapy / Q000201:enzymology*; D011817:Rabbits; D013936:Thymidine / Q000031:analogs & derivatives*; D013937:Thymidine Kinase / Q000172:deficiency*; D014271:Trifluridine / Q000627:therapeutic use*
D000998:Antiviral Agents; D005467:Floxuridine; C020235:brivudine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D014271:Trifluridine; D013936:Thymidine