Non-Linear Pharmacokinetics

Pharmacokinetic behavior in which key parameters such as clearance, volume of distribution, or bioavailability change with dose or concentration, violating the assumption of dose-proportional exposure. Non-linearity arises from saturation of metabolic enzymes, transporters, or protein binding. Drugs exhibiting non-linear kinetics require careful dose titration because small dose increases can produce disproportionately large changes in plasma concentration.

例

• Phenytoin: saturable CYP2C9 metabolism, small dose increases cause large concentration jumps
• Ethanol: zero-order elimination at typical blood alcohol concentrations
• Salicylates at high doses: saturation of glycine conjugation pathway