. .
.
Absorption and Distribution Property Prediction in Drug Designing Process
.
.

 

 

Procedure

 

For information on how to get the data, to access PreADMET with registration instructions, go to simulator tab 

 

Click on the link ADME Prediction in the home page, when it redirects to login page.

 

Figure 1: Screen shot of PreADMET home page

 

Login into the server to get redirected to the page for ADME prediction

 

Figure 2: Screenshot of interface forADME prediction

 

One can draw the chemical structure of the drug molecule using the tool bar in the white window as shown in the above screenshot (Figure 2)

 

Figure 3: Screenshot of toolbar to draw the compound strucutre

 

One can also import the structure of a molecule into the tool for predicting ADME. The structure of the molecule should be loaded in “mol” format.

 

 

Figure 4: Screenshot to import the molecule

 

Once the molecule is open and loaded, click on the calculate button seen at bottom right side of the window.

 

 Figure 5: Screenshot of the uploaded molecule

 

 

Calculating the ADME results

 

Here, one has options like calculate, reset, and clear result. By clicking “calculate” button, it will lead to calculation of ADME properties of a drug molecule. By clicking the reset button it will allow to reset the view of a drug molecule and clear result will clear the result page. It will allow loading of a new molecule without confusion. Results are shown below.

 

 

 Figure 6: Screenshot showing the results of absorption and distribution  prediction

 

AD prediction interpretation

 

There are several methods used in drug selection process to check for intestinal absorbtion. Caco-2 model and MDCK cell are referred to as invitro model for prediction of drug absorbtion, where the drug has been administered orally. PreADMET predicts the permeabilty of Caco-2 cell, MDCK cell, blood brain barrier, Human intestianl absorption, skin permeability and plasma protein binding.

 

Caco-2 cells are derived from human colon adenocarcinoma which has multiple drug transport pathways.

 

Caco-2 permeability in PreADMET  is classified into three classes.

 

  1.  If the permeability value is less than 4, then the molecule is having low permeability.
  2.  If the permeability value is between 4 to 70, then the molecule is having medium permeability.
  3.  If the permeability value is greater than 70, then the molecule is having higher permeability.

 

MDCK cell permeability

 

MDCK cell refers to Madin-Darby canine kidney cell. Since MDCK cells life span is less than the life span of Caco-2 cells, correlation between them is said to be high. MDCK cell system can be used as a good tool for rapid permeability screening.

 

MDK cell level of permeability in PreADMET can be classified into three classes,

 

1. If the permebiality value is less than 25, then the molecule is having low permeability.
2. If the permebiality value is between 25 to 500, then the molecule is having medium permeability.
3. If the permebiality value is greater than 500, then the molecule is having higher permeability.

 

Human intestinal absorption 

 

The intestinal absorption is very important to find the potential candidate and PreADMET finds the absorption in percentage. Poorly absorbed compounds return 0 to 20%, moderately absorbed compounds return 20- 70% and well absorbed compounds return 70-100%.

 

Skin permeability

 

Skin permeability factor is very important in case of cosmetics for transdermal delivery of drugs. PreADMET predicts the invitro skin permeability and the result is given as logKp.

 

Blood Brain Barrier

 

Predicting whether compounds pass across the blood-brain barrier is crucial in the pharmaceutical sphere because CNS-active compounds are the only substances which must cross the barrier. This happens in order to avoid CNS side effects in the brain. In PreADMET, one can predict rates for BBB penetration in vivo data.

 

PreADMET explains about the absorbtion to CNS as follows.

 

 Figure 7:  Absorption level in central nervous system

 

Plasma protein binding of a drug gives information on not only the drug action but also its efficacy and disposition.

 

In PreADMET, plasma protein binding capacity is referred to as

 

 

Figure 8: Binding capacity level interpretation table

 

 

This experiment uses : PreADMET, preadmet.bmdrc.org/ and Drugbank www.drugbank.ca/

 

Cite this Simulator:

.....
..... .....

Copyright @ 2018 Under the NME ICT initiative of MHRD

 Powered by AmritaVirtual Lab Collaborative Platform [ Ver 00.12. ]