What explains the difference in tissue distribution between thiopental and salicylic acid?

• A. Partition coefficient and acidity
• B. Molecular weight and volume
• C. Protein binding and metabolism
• D. pH alone

Answer: (A)

Tissue distribution is governed by two main properties: how well a drug dissolves in lipid membranes (lipophilicity, reflected by the partition coefficient) and how it ionizes at body pH (acidity or pKa). Thiopental is highly lipophilic, so it crosses membranes, including the blood-brain barrier, very readily and rapidly concentrates in the brain to produce its effect. As the brain quickly equilibrates, the drug then shifts into other tissues, especially fat, where its high lipid solubility leads to apparent redistribution and a shorter CNS effect.

Salicylic acid, on the other hand, is less lipophilic and is largely ionized at physiological pH. The ionized form crosses membranes poorly, so it distributes more slowly and does not accumulate in lipid-rich tissues as thiopental does. This difference in distribution is driven by partition coefficient and acidity, not by pH alone or by factors like protein binding or metabolism as the primary explanation.