Free drug levels can generally be determined by analyzing what body fluid?

• A. Whole blood
• B. Ultrafiltrate of plasma
• C. Urine
• D. Protein-free filtrate of plasma

Answer: (B)

Free drug levels reflect the unbound fraction of a drug in plasma, which is the portion that can exert pharmacologic effects and move into tissues. In plasma, drugs bind to proteins like albumin; the bound portion is large and stays with the proteins, while only the unbound portion can pass through a membrane. Ultrafiltration of plasma uses a semipermeable membrane to separate this unbound drug into a filtrate, leaving the protein-bound drug behind. Analyzing that ultrafiltrate gives the true free concentration, which is why it’s the best sample for measuring free drug levels. Whole blood includes cells and can distort the free fraction; urine reflects what’s been filtered and excreted rather than the plasma free concentration; the protein-free filtrate of plasma is essentially the same idea as the ultrafiltrate, but the standard, widely used term is ultrafiltrate of plasma.