Preclinical studies of iododeoxuridine in dimethyl sulfoxide for the topical treatment of cutaneous herpes simplex virus infections

Abstract

The topical use of iododeoxyuridine (IDU) in dimethyl sulfoxide (DMSO) for the treatment of cutaneous herpes simplex virus (HSV) infections has been advocated for over 20 years, but the clinical efficacy of this combination remains controversial. The following studies were undertaken to understand better how variable formulations of IDU in DMSO and different rates of percutaneous drug delivery affect clinical efficacy. The flux of IDU from DMSO through excised guinea pig skin was measured in Franz diffusion cells, with varying experimental conditions and formulations of IDU, DMSO and water. Contrary to predictions derived from Fick's law, the flux of IDU did not continue to increase with increasing drug concentration beyond 20% IDU. Higher rates of drug flux were measured when the in vitro experimental conditions more closely replicated those of a skin surface in vivo, that is with the receiver solution at 37°C and skin exposed to ambient conditions. Three IDU-DMSO formulations tested in vitro were used to treat an experimental dorsal cutaneous HSV infection of guinea pigs. The flux values determined at 37°C in the open diffusion cells showed better correlation with treatment efficacy. The results of these experiments may explain in part why very high concentrations of IDU in DMSo may not necessarily be more clinically effective beyond an optimal drug concentration and why results with different IDU-DMSO formulations have been variable.