Efficacy of (S)-HPMPA against thymidine kinase-deficient herpes simplex virus-keratitis.
A new acyclic adenosine analogue, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], was evaluated for its efficacy in the topical treatment of experimental keratitis caused by the thymidine kinase-positive (TK+) and thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. In the treatment of TK+ HSV-1 keratitis, 0.2% (S)-HPMPA eyedrops were as effective as the reference compounds, 0.2% (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 0.2% 5-(2-chloroethyl)-2'-deoxy-uridine (CEDU) eyedrops. The three compounds produced a statistically significant healing effect, as compared with placebo eyedrops. In the treatment of keratitis caused by the TK- HSV-1 strain, 0.2%BVDU and 0.2% CEDU eyedrops did not differ from placebo eyedrops, whereas 0.2% (S)-HPMPA eyedrops exerted a highly significant healing effect.
Maudgal
P C
PC
Eye Research Laboratory, Ophthalmological Clinic, Katholieke Universiteit, Leuven, Belgium.
De Clercq
E
E
Huyghe
P
P
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D003857:Deoxyuridine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000473:pathology; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013937:Thymidine Kinase / Q000378:metabolism*
D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C020235:brivudine; C047370:5-(2-chloroethyl)-2'-deoxyuridine; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D000225:Adenine; D003857:Deoxyuridine