Fundamental Pharmacokinetic Concepts and Their Clinical Relevance: Clearance, Zero Versus First Order and Nonlinear Pharmacokinetics

In response to a question posed by a valued colleague, this column will discuss 4 fundamental pharmacokinetic concepts: (1) What does the term clearance encompass? (2) What do the terms first order and second order pharmacokinetics mean? (3) What does the term nonlinear pharmacokinetics mean and is it just a synonym for zero order pharmacokinetics? (4) What is the clinical relevance, if any, of these concepts and why? In addition, this column cites several earlier columns that are relevant to aspects of each of the answers. Thus, readers interested in more details can refer to these earlier publications that include case examples and figures that further illustrate various points. In considering the clinical relevance of these pharmacokinetic concepts, this column discusses relative binding affinity for targets and the concept of selective versus nonselective drugs, which are foundational cornerstones for understanding and optimally using currently available psychopharmaceutical agents.