In first-order elimination, which parameter is typically constant across the therapeutic concentration range?

• A. Clearance
• B. Volume of distribution
• C. Absorption rate constant
• D. Bioavailability

Answer: (A)

In first-order elimination, the body's ability to clear drug is not saturated within the therapeutic range, so the rate of removal is proportional to how much drug is present. The constant that governs this proportionality is clearance, a systemic parameter that represents the volume of plasma cleared of drug per unit time. Because the elimination pathways (like liver metabolism and kidney excretion) aren’t maxed out at therapeutic concentrations, clearance stays essentially the same as concentration changes, making the elimination rate simply CL × C. The other parameters describe different processes: absorption rate constant and bioavailability relate to how much drug enters circulation, while volume of distribution reflects how the drug distributes between plasma and tissues and can vary with concentration or physiological state. Therefore, clearance is the parameter that remains constant across the therapeutic concentration range in first-order elimination.