Influence of 1-dodecylazacycloheptan-2-one (Azone) on the topical therapy of cutaneous herpes simplex virus type 1 infection in hairless mice with 2',3'-di-O-acetyl-9-beta-D-arabinofuranosyladenine and 5'-O-valeryl-9-beta-D-arabinofuranosyladenine.
The predictive value of a recently developed physical model was tested in the topical treatment of cutaneous infections caused by herpes simplex virus type 1 in hairless mice with two ester prodrugs of 9-beta-D-arabinofuranosyladenine (ara-A) (1). The tests were conducted with 2',3'-di-O-acetyl-ara-A (4) and 5'-O-valeryl-ara-A (3) topically applied with and without 15% 1-dodecylazacycloheptan-2-one (2) (Azone), a percutaneous penetration enhancer. In addition to the in vivo studies, in vitro diffusion cell experiments with excised, full-thickness skin from hairless mice were conducted to determine the penetration enhancement effects of 2. As previously observed, 2 was able to induce remarkably large (100- to 1000-fold) flux enhancements in these in vitro experiments. Consistent with predictions based on the physical model studies, formulations of 3 and 4 without 2 had little or no influence on the pathogenesis of the herpes simplex virus type 1 infections; when 2 was present in the formulations, both 3 and 4 had dramatic therapeutic effects consistent with the predictions made with the physical model. Prodrug 4 with 2 was especially efficacious in the prevention of virus-induced lesions and in the survival of all animals. Similar results were obtained with acyclovir plus 2 in this model system.
D000212:Acyclovir / Q000627:therapeutic use; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001381:Azepines / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004058:Diffusion; D006561:Herpes Simplex / Q000188:drug therapy*; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D012869:Skin Absorption; D013997:Time Factors; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000998:Antiviral Agents; D001381:Azepines; C035229:laurocapram; C034898:vidarabine 2',3'-diacetate; C026073:vidarabine 5'-valerate; D014740:Vidarabine; D000212:Acyclovir