brivudine and Skin-Diseases

In a prospective open trial 40 patients suffering from acute herpes zoster ophthalmicus were treated with systemic acyclovir. An additional 10 patients were treated by topical acyclovir alone and dexamethasone eye-drops were administered to 5 of them to suppress ocular inflammation. In the topical treatment group the period of new skin lesion formation and progression of ocular inflammatory signs were significantly prolonged. Therapy with systemic acyclovir however resulted in a quick and complete resolution of ocular inflammation in all patients. Chronic ocular inflammation developed in 4 out of 10 patients treated with topical acyclovir. We consider chronic ocular zoster as a distinct clinical entity, possibly expressing a failing local immune response against VZV.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Bromodeoxyuridine; Chronic Disease; Conjunctivitis; Dexamethasone; Drug Administration Routes; Female; Herpes Zoster Ophthalmicus; Humans; Keratitis, Dendritic; Male; Middle Aged; Prospective Studies; Scleritis; Skin Diseases; Uveitis, Anterior

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.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Bromodeoxyuridine; Deoxyuridine; Diffusion; Female; Guinea Pigs; Herpes Simplex; Idoxuridine; Pharmaceutical Vehicles; Skin Diseases; Trifluridine; Vidarabine