Note on drug absorption

They mostly use the computer to find the relative pattern between chemical features and physico-chemical properties.

For example,

Using atom-based calculation  -- > partition coefficient (log P) which tells you the cell permeability -- this is an important feature for drug development, especially for orally administered drugs.

Absorption is affected by solubility and permeability.

Lipophilicity -- a ratio of octanol solubility to aqueous solubility

High-throughput screening started in 1989.

The reason why they came up with the rule of 5 -- 

• To reduce the failure rate during phase I development which concerns the safety

• To reduce poor solubility and permeability

• MW < 500 kDa

• LogP < 5

• HbondDonor < 5

• HbondAccept >10

• If two parameters are out of range -- likely to be poor absorption and permeability

Ref: 

1. Prediction of Physicochemical Parameters by Atomic Contributions (doi: 10.1021/ci990307l)

2. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings (doi: 10.1016/s0169-409x(00)00129-0)