Drug Absorption and Distribution Practice Test 2026 – The Complete Guide to Mastering Your Exam Success!

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If a drug is highly bound to plasma proteins, what is the expected free fraction?

It is large.

It is relatively small; only a portion is unbound.

The main idea here is plasma protein binding and how it governs the unbound, pharmacologically active portion of a drug. When a drug binds strongly to plasma proteins, only a small portion remains free in the bloodstream. The unbound fraction is the portion that can exert effects, distribute into tissues, and be cleared by the liver or kidneys. Because binding creates a dynamic equilibrium, as free drug is cleared, more drug can dissociate from the protein to replace it, but the free fraction stays relatively small overall for a highly bound drug. So, the expected free fraction is small, with most of the drug tied up in protein binding.

In other words, a large free fraction would imply weak or little binding; a zero free fraction isn’t realistic because there’s always some unbound drug at equilibrium; and the concept isn’t inherently unpredictable—binding tends to be determined by the drug’s affinity for the protein and its concentration, though factors like interactions with other drugs or disease states can shift it.

It remains zero always.

It is unpredictable.

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