Chapter 2: Pharmacokinetics or What the Body Does to the Drug

Pharmacokinetics or What the Body Does to the Drug overview provides a comprehensive analysis of pharmacokinetics, the branch of pharmacology defined as the study of drug disposition or what the body does to the drug. The content is rigorously structured around the four fundamental processes known as ADME: absorption, distribution, metabolism, and excretion. The summary begins by exploring drug absorption, explaining how therapeutic agents cross biologic barriers through passive diffusion, facilitated diffusion, and active transport, while highlighting how the physical characteristics of a drug and the pH of the environment influence ionization and membrane penetration based on the Henderson-Hasselbalch relationship. The discussion moves to drug distribution, examining how blood flow to various organs, plasma protein binding to albumin and glycoproteins, and specific barriers like the blood-brain barrier dictate where drugs localize in the body. It also defines the volume of distribution as a theoretical parameter relating drug dose to plasma concentration. A major focus is placed on metabolism, or biotransformation, detailing the liver's role in converting lipophilic drugs into water-soluble metabolites through Phase I reactions—mediated largely by the cytochrome P450 monooxygenase system—and Phase II conjugation reactions. The text further explains the first-pass effect, the impact of genetic polymorphisms on enzyme activity, and the concept of prodrugs. The excretion section outlines how the kidneys eliminate drugs via glomerular filtration, active tubular secretion, and passive reabsorption, alongside biliary excretion and enterohepatic cycling. Finally, the chapter elucidates quantitative pharmacokinetics, distinguishing between first-order and zero-order kinetics, and defining critical clinical metrics such as bioavailability, clearance, elimination half-life, steady-state concentrations, and the calculations required for loading and maintenance doses.