How does the partition coefficient logP relate to distribution into fat and the Vd?

• A. Higher logP (more lipophilic) promotes fat accumulation and higher Vd due to tissue partitioning.
• B. Lower logP leads to higher Vd.
• C. logP does not affect distribution.
• D. logP only affects plasma protein binding.

Answer: (A)

Lipophilicity drives how widely a drug distributes into body tissues. Higher logP means the molecule is more fat-loving and readily partitions into lipid-rich tissues, including fat. As more drug moves out of the plasma and into tissues, the plasma concentration for a given dose drops, which makes the volume of distribution (Vd) larger, since Vd = dose / plasma concentration. So increasing logP tends to increase distribution into fat and raise Vd. Conversely, less lipophilic compounds stay more in aqueous compartments and in plasma, yielding a smaller Vd. While plasma protein binding and other factors also influence distribution, the main link here is that greater lipophilicity promotes tissue partitioning and a higher Vd.