In a receptor-saturable system, what happens to Cmax and AUC as dose increases from low to high within the same individuals?

• A. Cmax and AUC increase linearly with dose
• B. Cmax and AUC may increase less than proportionally at high doses due to saturation
• C. Both increase more than proportionally
• D. Cmax decreases while AUC increases

Answer: (B)

When a system is receptor-saturable, there is a finite number of binding sites or transport processes that mediate drug entry or effect. At low doses, many receptors are free, so increasing dose yields a roughly proportional rise in amount absorbed and in plasma concentration, making Cmax and AUC scale more or less with dose. But as dose increases and receptors become occupied, the rate-limiting step can no longer accelerate with dose. The uptake or exposure cannot keep climbing in lockstep with dose, so Cmax rises more slowly and the total exposure, AUC, also increases by a smaller amount than the dose. In other words, Cmax and AUC may increase less than proportionally as you move from low to high doses within the same individual.