Under repeated dosing, which kinetic profile is most likely to lead to drug accumulation and toxicity?

Under repeated dosing, which kinetic profile is most likely to lead to drug accumulation and toxicity?

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

Answer: (A)

Zero-order elimination removes a constant amount of drug per unit time, regardless of how much is in the body. When dosing is repeated, this fixed removal rate cannot increase to match the ongoing input, so drug accumulates with each dose and plasma concentrations rise toward toxic levels. In first-order kinetics, elimination speeds up as concentration rises, and a steady state is reached after a few half-lives, preventing indefinite buildup. Saturable or mixed-order kinetics can also lead to non-linear increases once capacity is exceeded, but the scenario that most directly leads to accumulation and toxicity is the constant, capacity-limited removal of zero-order kinetics.

Zero-order elimination removes a constant amount of drug per unit time, regardless of how much is in the body. When dosing is repeated, this fixed removal rate cannot increase to match the ongoing input, so drug accumulates with each dose and plasma concentrations rise toward toxic levels. In first-order kinetics, elimination speeds up as concentration rises, and a steady state is reached after a few half-lives, preventing indefinite buildup. Saturable or mixed-order kinetics can also lead to non-linear increases once capacity is exceeded, but the scenario that most directly leads to accumulation and toxicity is the constant, capacity-limited removal of zero-order kinetics.