Skin Permeability

In the pharmaceutical, cosmetic and agrochemical fields, it is important to predict the skin permeability rate for a crucial parameter for the transdermal delivery of drugs and for the risk assessment of all chemicals that come into contact with the skin either accidentally or by design. In PreADMET can predict in vitro data on human for skin permeability.

PreADMET predicts in vitro skin permeability and the result value is given as logKp. Kp (cm/hour) is defined as:

Kp= Km*D/h

 

where Km is distribution coefficient between stratum corneum and vehicle, and D is average diffusion coefficient (cm2/h), and h is thickness of skin (cm).

[ Singh,S. et al. Med. Res. Rev. 1993, 13, 569. ]

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Human Intestinal Absorption

Predicting human intestinal absorption of drugs is very important for identify potential drug candidate. In PreADMET can predict percent human intestinal absorption (%HIA). Human intestinal absorption data are the sum of bioavailability and absorption evaluated from ratio of excretion or cumulative excretion in urine , bile and feces.

[ Zhao,Y.H. et al. J. Pharm. Sci. 2001, 90, 749. ]

 

For prediction of HIA in PreADMET, chemical structures at pH 7.4 are applied, because HIA is measured by in vivo test. This is one of options of PreAMDET and user can choose for this option.

 

Although there are some differences in the experimental values by compounds or their metabolisms, we can put into general categories like below.

[ Yee,S. Pharm. Res. 1997, 14, 763. ]

 

Classification HIA (Human Intestinal Absorption)
Poorly absorbed compounds 0 ~ 20 %
Moderately absorbed compounds 20 ~ 70 %
Well absorbed compounds 70 ~ 100 %
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Caco2 cell permeability

Numerous in vitro methods have been used in the drug selection process for assessing the intestinal absorption of drug candidates. Among them, Caco-2 cell model and MDCK cell model has been recommended as a reliable in vitro model for the prediction of oral drug absorption.

[ Yamashita,S. et al. Eur. J. Pharm. 2000, 10, 195. ]

Caco-2 cells are derived from human colon adenocarcinoma and possess multiple drug transport pathways through the intestinal epithelium.

For prediction of Caco-2 cell permeability in PreADMET, chemical structures at pH 7.4 are applied, because Caco-2 cell permeability and MDCK cell permeability are measured at about pH 7.4. This is one of options of PreAMDET and user can choose for this option.

Although there are some differences in the experimental values by compounds or their metabolisms, we can put into general categories like below.

[ Yazdanian,M. Pharm. Res. 1998, 15(9), 1490. ]

Classification PCaco-2 (nm/sec)
Low permeability less than 4
Middle permeability 4 ~ 70
High permeability more than 70

[ (1) Yamashita,S. et al. Eur. J. Pharm. Sci. 2000, 10, 195., (2) Irvine,J.D. et al. J. Pharm. Sci. 1999, 88, 28. ]

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