Prediction of human percutaneous absorption from in vitro and in vivo animal experiments
Autor: | Hiromichi Yoshimatsu, Kunikazu Ishii, Shinji Yamashita, Yoshihiro Konno, Masahiro Satsukawa |
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Rok vydání: | 2017 |
Předmět: |
Animal Experimentation
Male 0301 basic medicine Swine Skin Absorption Combined use Pharmaceutical Science Pharmacology Administration Cutaneous 030226 pharmacology & pharmacy Permeability Mice 03 medical and health sciences 0302 clinical medicine Pharmacokinetics In vivo Animals Humans Medicine Skin Mice Hairless Drug permeation business.industry In vivo absorption Middle Aged In vitro Rats 030104 developmental biology In vitro permeation Pharmaceutical Preparations Percutaneous absorption Swine Miniature business |
Zdroj: | International Journal of Pharmaceutics. 534:348-355 |
ISSN: | 0378-5173 |
DOI: | 10.1016/j.ijpharm.2017.10.048 |
Popis: | 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. |
Databáze: | OpenAIRE |
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