Will a very lipophilic drug administered via inhalation be found in the bloodstream?

• A. It will be found in the blood in high amounts
• B. It will be found in the blood only after redistribution
• C. It will be present at moderate levels in blood due to diffusion
• D. It is unlikely to be found in the blood because it is already in tissue

Answer: (D)

High lipophilicity drives extensive tissue distribution. When a drug is very lipophilic and delivered by inhalation, it quickly partitions into lipid-rich tissues, including lung tissue, rather than remaining in the plasma. This creates a large volume of distribution and leaves only small amounts in the blood at any given time. So, despite fast entry from the lungs into circulation, most of the drug is sequestered in tissue, making bloodstream levels unlikely to be high.