title: (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine in the therapy of thymidine kinase-positive and -deficient herpes simplex virus experimental keratitis.
abstract: The phosphonylmethoxyalkyl derivative, (S)-1-(3-hydroxy-2-phosphonyl methoxypropyl)cytosine (HPMPC), was evaluated for its efficacy in the topical treatment of experimental keratitis caused by thymidine kinase-positive (TK+) or thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. The HPMPC 0.2% eyedrops were as effective as the reference compound, (E)-5-(2-bromovinyl)-2'-deoxyuridine, (BVDU) 0.2% eyedrops in stimulating the healing of epithelial disease caused by the HSV-1 TK+ strain. Both drugs achieved a significant (P less than 0.005) healing effect compared with placebo eyedrops. No significant differences were noted in the efficacy of HPMPC 0.2% eyedrops when instilled one, three, or nine times a day. In the treatment of keratitis caused by the HSV-1 TK- strain, 0.2% BVDU eyedrops were similar to placebo; 0.2% HPMPC eyedrops again had a brisk and significant healing effect (P less than 0.005).
authors.affiliation: Eye Research Laboratory, Katholieke Universiteit Leuven, Belgium.
authors.forename: P C
authors.initials: PC
authors.lastname: Maudgal
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007635:Keratitis, Dendritic / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C020235:brivudine; D003596:Cytosine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D000077404:Cidofovir