Efficacy of topical treatment for herpes simplex virus infections: predictions from an index of drug characteristics in vitro.
Topical antiviral treatments for recurrent infection with herpes simplex virus in immunocompetent patients have been generally ineffective. We investigated whether in vitro drug measures could predict in vivo efficacy. Twelve topical antiviral formulations were evaluated in vitro by measuring inhibition of viral plaque formation in cell culture (ID50) and drug penetration through excised guinea pig skin. In vivo efficacy for each treatment was determined in an experimental cutaneous infection with herpes simplex virus type 1 in guinea pigs and expressed as the percent reduction in lesion number, lesion area, and virus titer in the lesions. The in vitro findings were correlated with the results in the animal model. ID50 was a poor predictor of in vivo efficacy, whereas stronger correlations were found between the degree of skin penetration and in vivo activity. The best correlation was noted by using a summary expression of the in vitro results as follows: the ratio of drug penetration through skin at 37 C to ID50 (r = .95, .94, and .92 for lesion number, area, and virus titer, respectively, P less than .0005). Determination of this in vitro index should be included in the preclinical evaluation of new topical antiviral formulations.
Freeman
D J
DJ
Spruance
S L
SL
D000212:Acyclovir / Q000008:administration & dosage; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003857:Deoxyuridine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004058:Diffusion; D005260:Female; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000188:drug therapy*; D007065:Idoxuridine / Q000008:administration & dosage; D014677:Pharmaceutical Vehicles; D012871:Skin Diseases / Q000188:drug therapy; D014271:Trifluridine / Q000008:administration & dosage; D014740:Vidarabine / Q000008:administration & dosage
D000998:Antiviral Agents; D014677:Pharmaceutical Vehicles; C022811:edoxudin; C020235:brivudine; D014740:Vidarabine; D001973:Bromodeoxyuridine; D007065:Idoxuridine; D014271:Trifluridine; D003857:Deoxyuridine; D000212:Acyclovir