What occurs when the plasma concentration of a drug exceeds the $K_m$ (Michaelis constant) of its primary metabolic enzyme?

Correct answer: The rate of metabolism becomes zero-order

When concentration ($C$) is much greater than $K_m$, the enzymes are working at their maximum capacity ($V_{max}$). At this point, the elimination rate is constant (zero-order), and small dose increases can lead to disproportionate rises in plasma levels.