Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences)
Online ISSN : 1882-1499
Print ISSN : 1346-342X
ISSN-L : 1346-342X
Regular Articles
Preclinical Study of Tacrolimus Ointment for Prevention of Its Systemic Absorption in Atopic Dermatitis Model Mice According to Their Skin Conditions
Yutaro HazamaWataru UchidaToshihisa MaekawaRyotaro MikiShinji OshimaYuya EgawaOsamu HosoyaToshinobu Seki
Author information

2017 Volume 43 Issue 9 Pages 477-491


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.

Content from these authors
© 2017 Japanese Society of Pharmaceutical Health Care and Sciences
Next article