抄録
Tacrolimus (TL) is used topically for atopic dermatitis (AD) treatment. In AD, the skin shows various physiological alterations across individuals, body sites, and time-courses. Our previous study using rats showed that alterations in the skin barrier function and skin blood flow affected systemic absorption of topically applied TL. In this study, we performed an in vivo skin absorption study using NC/Nga mice repeatedly administered Dermatophagoides farinae extract as an AD animal model to assess skin barrier function and skin blood flow. We used three types of TL ointment: or iginal TL ointment (Protopic® 0.1％ ointment) and liquid paraffin-diluted TL ointment with or without adrenaline (0.5w /w％) to suppress systemic absorption of TL. Skin barrier function correlated positively with the systemic absorption of TL in AD skin as well as in tape-stripped rat skin, and dilution of TL ointment suppressed TL absorption and showed high skin TL retention. Although skin blood flow affected TL absorption as the skin barrier was disrupted, the distinct relationship among skin blood flow, TL absorption, and the effect of combined-use of adrenaline was unclear. The relationship between blood and skin disposition of TL was biphasic—the ratio of blood to skin disposition increased rapidly at an inflection point. These results demonstrate that the dilution of TL ointment is useful for increasing treatment safety while retaining efficacy. The observed relationship between TL behavior and skin barrier function in AD model mice may also occur in AD patients and needs to be confirmed in further studies.
