Which statement best explains why thiopental reaches CSF equilibrium faster than salicylic acid?

• A. It is highly lipophilic and unionized at physiological pH
• B. It has a higher molecular weight
• C. It is ionized at physiological pH
• D. It has a lower partition coefficient

Answer: (A)

Diffusion into CSF relies on how readily a drug can cross lipid membranes. Drugs that are highly lipophilic and largely unionized at physiological pH cross the blood–brain barrier by passive diffusion much more quickly, so they reach CSF equilibrium faster. Thiopental fits this pattern: it is very lipophilic and remains largely nonionized at pH 7.4, allowing rapid diffusion into CNS compartments and swift equilibration with CSF. Salicylic acid, on the other hand, is mostly ionized at physiological pH (carboxylate form), which greatly reduces its membrane permeability, slowing its entry into CSF. Factors like higher molecular weight or a lower partition coefficient would also hinder diffusion. So the key reason is the combination of high lipophilicity and unionized state at physiological pH for thiopental.