There are several causes of non-linearity in pharmacokinetics, key among them being:
Saturation of Metabolic Pathways: At high drug concentrations, metabolic enzymes may become saturated, leading to a disproportionate increase in drug levels. Transporter Saturation: Similar to enzymes, drug transporters responsible for absorption, distribution, or excretion can also reach saturation, affecting drug disposition. Protein Binding: Changes in the degree of protein binding at different concentrations can result in non-linear pharmacokinetics. Auto-Induction or Inhibition: Drugs that induce or inhibit their own metabolism can lead to time-dependent changes in pharmacokinetics.
