What does it mean if a drug is highly polar?

When a drug is described as highly polar, it means that the molecule has a significant distribution of electrical charge, leading to hydrophilicity or water solubility. This property fundamentally impacts how the drug interacts with biological membranes, which are primarily composed of lipid bilayers.

Lipid membranes act as barriers that are more permeable to non-polar (lipophilic) substances than to polar molecules. As a highly polar drug has difficulty interacting with and passing through these lipid membranes, it typically has a lower ability to cross them. Therefore, this characteristic often results in reduced absorption and penetration into tissues that are rich in lipid components, which is crucial for drug bioavailability and distribution.

In contrast, non-polar (or lipophilic) drugs can easily cross lipid membranes and reach their target sites more readily. This is why understanding a drug's polarity is essential for predicting its pharmacokinetic behavior, including absorption, distribution, metabolism, and excretion.