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A Strategy for in Silico Prediction of the Membrane Permeability of Drugs
- Source :
- Bulletin of the Chemical Society of Japan. 91(11):1618-1624
- Publication Year :
- 2018
- Publisher :
- Chemical Society of Japan, 2018.
-
Abstract
- Parallel artificial membrane permeation assay (PAMPA) was performed for nine amine drugs and their permeability coefficient (logP(pampa)) was determined at different pH's. The previously developed digital simulation method was successfully used to reproduce the sigmoid-like pH dependence of log P-pampa, and the distribution coefficient (log K-D,K-M) to the lipid-containing dodecane membrane could be determined for all the amine drugs studied. The thus determined log K-D,K-M values showed a linear free-energy relationship with the standard ion-transfer potential (Δ(W)(O)??∘; R2 = 0.754) and the distribution coefficient (logK(D); R-2 = 0.891), which were previously determined by ion-transfer voltammetry with the 1,2-dichloroethane|water interface. On the other side, we can predict Δ(W)(O)??∘ very accurately by a previously proposed solvation model called the "non-Bornian" model. These findings suggest a possible strategy for perfect in silico prediction of the membrane permeability of drugs.
- Subjects :
- Chromatography
Membrane permeability
Chemistry
In silico
Synthetic membrane
non-Bornian model
General Chemistry
Permeability coefficient
Permeation
010402 general chemistry
030226 pharmacology & pharmacy
01 natural sciences
0104 chemical sciences
PAMPA
03 medical and health sciences
0302 clinical medicine
Amine gas treating
Digital simulation
Subjects
Details
- Language :
- English
- ISSN :
- 00092673
- Volume :
- 91
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Bulletin of the Chemical Society of Japan
- Accession number :
- edsair.doi.dedup.....6a5145c66c0ffd032c2b636a266e7d91