What happens to the free drug concentration when plasma albumin decreases?

• A. Decreases
• B. Increases
• C. Stays the same
• D. Becomes inactive

Answer: (B)

When plasma albumin decreases, there is less binding capacity for drugs that rely on albumin for protein binding. The portion of the drug that is not bound to albumin—the free fraction—increases. Since it is the unbound drug that is pharmacologically active and available for distribution to tissues and for elimination, the free drug concentration rises as albumin falls. Keep in mind that this can also lead to faster clearance of the drug because the unbound form is cleared more readily, which can influence total drug levels over time. This effect is most pronounced for drugs that are highly albumin-bound; drugs with little or no albumin binding won’t show this shift as much.