Cutaneous distribution of orally administered itraconazole in guinea pigs, studied by autoradiography

Background Itraconazole is an orally active antifungal lipophilic drug with high affinity for sebum and keratinocytes. Aim The aim of the study was to investigate the routes of percutaneous egression and the sites of cutaneous action/storage of 3H-labelled itraconazole in an experimental animal model. Material and methods Hartley guinea pigs were dosed orally by gavage for 2 consecutive days at 10 mg/kg/day 3H-itraconazole dissolved in polyethylene glycol 200. At various time points after the second gavage, small full-thickness samples of dorsal skin were excised and processed using dry-apposing autoradiography. Results Our research revealed an accumulation of silver grains over the epidermis and its appendages (hair follicle and sebaceous gland), the dermal fat tissue and the hypodermal muscle tissue on tissue sections at 6, 24 and 48 h time intervals, whereas at the remaining time points (96, 168 and 336 h) the silver grain density was markedly decreased to background level. Discussion The present histological distribution data support the current method of oral treatment with itraconazole as the treatment schedule of choice to eradicate infective organisms residing in the deeper skin layers.