If dosing rate exceeds elimination capacity in zero-order kinetics, how does plasma concentration change over time?

If dosing rate exceeds elimination capacity in zero-order kinetics, how does plasma concentration change over time?

• A. It remains steady
• B. It declines exponentially
• C. It increases linearly without bound
• D. It fluctuates unpredictably

Answer: (C)

In zero-order kinetics, the body removes drug at a constant amount per unit time, regardless of how much drug is present. If you dose at a rate higher than this constant elimination capacity, the drug is added faster than it can be cleared. The net rate of change of the drug in the body is positive and constant (input rate minus the constant elimination rate). Because this net rate is constant, the amount of drug in the body increases linearly with time, and with a relatively constant volume of distribution, the plasma concentration also rises linearly. This rise would continue without bound as long as the dosing rate remains higher than the elimination capacity and the saturation conditions persist.

In zero-order kinetics, the body removes drug at a constant amount per unit time, regardless of how much drug is present. If you dose at a rate higher than this constant elimination capacity, the drug is added faster than it can be cleared. The net rate of change of the drug in the body is positive and constant (input rate minus the constant elimination rate). Because this net rate is constant, the amount of drug in the body increases linearly with time, and with a relatively constant volume of distribution, the plasma concentration also rises linearly. This rise would continue without bound as long as the dosing rate remains higher than the elimination capacity and the saturation conditions persist.