What is LogP and Why Do Drug Designers Care?

LogP measures the partition coefficient of a compound between octanol and water, indicating how hydrophobic or hydrophilic it is. A LogP of 0 means equal solubility in both. Positive values indicate lipophilicity (fat-solubility), while negative values indicate hydrophilicity. Drug designers use LogP to predict absorption, distribution, metabolism, and excretion.

Lipinskis Rule of Five suggests LogP should not exceed 5 for oral drugs. Too lipophilic and the drug gets trapped in membranes. Too hydrophilic and it cannot cross them..