Prediction of human percutaneous absorption from in vitro and in vivo animal experiments

[Display omitted] Although anatomical and structural similarities between the skin of minipigs and humans are often reported, few percutaneous pharmacokinetic studies have been conducted in minipigs. The objective of this study was to clarify the usefulness of minipigs for estimating the percutaneou...

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Bibliographic Details
Published in:International journal of pharmaceutics 2017-12, Vol.534 (1-2), p.348-355
Main Authors: Yoshimatsu, Hiromichi, Ishii, Kunikazu, Konno, Yoshihiro, Satsukawa, Masahiro, Yamashita, Shinji
Format: Article
Language:English
Subjects:
Administration, Cutaneous
Animal Experimentation
Animals
Humans
Male
Mice
Mice, Hairless
Middle Aged
Minipig
Percutaneous absorption
Permeability
Pharmaceutical Preparations - metabolism
Predicting human PK
Rats
Skin - metabolism
Skin Absorption - physiology
Skin permeation
Swine
Swine, Miniature
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Summary:[Display omitted] Although anatomical and structural similarities between the skin of minipigs and humans are often reported, few percutaneous pharmacokinetic studies have been conducted in minipigs. The objective of this study was to clarify the usefulness of minipigs for estimating the percutaneous absorption of various drugs in humans. The absorption of several marketed drugs was observed in mice, rats and minipigs both in vivo and in vitro, and results were compared with those in humans. For all six model drugs, after percutaneous administration in vivo, fraction of dose absorbed (F) from the skin was the lowest in minipigs among the four species studied, including humans. In vitro drug permeation results were similar, with the lowest permeability observed in minipigs. However, combined use of both in vitro permeation and in vivo absorption data from minipigs using triple pack approach resulted in better prediction of human F values than data obtained from mice. These results suggest some qualitative, but not quantitative, similarities between the drug absorption process across the skin of minipigs and humans. In conclusion, minipigs appear to be a promising model animal for predicting percutaneous drug absorption in humans, however, more in vivo and in vitro studies are needed to improve predictability.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2017.10.048