Hydrophobicity

The tendency of a molecule or molecular region to be repelled by water and associate with non-polar environments, quantified by the partition coefficient (logP) or distribution coefficient (logD). Hydrophobicity is a primary determinant of membrane permeability, plasma protein binding, volume of distribution, and metabolic susceptibility. Optimal hydrophobicity for oral drugs typically falls in the logP range of 1-3.

Ví dụ

• Amiodarone: highly hydrophobic (logP ~7.6), accumulates extensively in adipose tissue (Vd ~66 L/kg)
• Atenolol: hydrophilic (logP ~0.2), limited CNS penetration (fewer central side effects)
• Itraconazole: highly lipophilic (logP ~5.7), requires cyclodextrin formulation for solubility