Which type of kinetics is more likely to result in drug toxicity under repeated dosing?

Which type of kinetics is more likely to result in drug toxicity under repeated dosing?

• A. Zero-order kinetics
• B. First-order kinetics
• C. Mixed-order kinetics
• D. Saturable kinetics

Answer: (A)

Zero-order elimination means a constant amount of drug is cleared per unit time, regardless of how much is in the body. With repeated dosing, this fixed removal rate can’t increase to match higher concentrations, so each new dose adds to the leftover drug from earlier doses. Over time, plasma levels build up and can reach toxic levels because the body isn’t able to speed up clearance as concentration rises. In contrast, first-order elimination clears a larger amount as concentrations rise, leading to a predictable steady state and less risk of accumulation-driven toxicity. Nonlinear or saturable kinetics can cause unpredictable increases, but the direct driver of toxicity with repeated dosing is the constant, concentration-insensitive clearance seen in zero-order kinetics.

Zero-order elimination means a constant amount of drug is cleared per unit time, regardless of how much is in the body. With repeated dosing, this fixed removal rate can’t increase to match higher concentrations, so each new dose adds to the leftover drug from earlier doses. Over time, plasma levels build up and can reach toxic levels because the body isn’t able to speed up clearance as concentration rises. In contrast, first-order elimination clears a larger amount as concentrations rise, leading to a predictable steady state and less risk of accumulation-driven toxicity. Nonlinear or saturable kinetics can cause unpredictable increases, but the direct driver of toxicity with repeated dosing is the constant, concentration-insensitive clearance seen in zero-order kinetics.