Abstract

Nonlinear pharmacokinetics is a phenomenon observed in drug metabolism, where the relationship between drug concentration and time is not proportional due to saturable processes or complex interactions within the body. Understanding the intricacies of nonlinear pharmacokinetics is crucial for optimizing drug dosing regimens, predicting drug interactions, and ensuring therapeutic efficacy and safety. This review aims to provide a comprehensive overview of nonlinear pharmacokinetics, focusing on the mechanisms underlying nonlinear behavior and the implications for drug development and clinical practice. We discuss various factors that contribute to nonlinear pharmacokinetics, including saturable absorption, protein binding, enzyme saturation, and active transport systems. Additionally, we explore mathematical models and simulation techniques used to characterize and predict nonlinear pharmacokinetics, highlighting their advantages and limitations. Moreover, we discuss the challenges associated with studying nonlinear pharmacokinetics, such as interindividual variability and drug-drug interactions. Finally, we present case examples of drugs exhibiting nonlinear pharmacokinetics and discuss strategies for optimizing dosing regimens in these scenarios. Overall, this review provides a comprehensive understanding of nonlinear pharmacokinetics and emphasizes the importance of considering this phenomenon in drug development and therapeutic decision-making.