An Introduction to Safety Pharmacokinetics

Pharmacokinetics is a field within pharmacology that studies the movement of a xenobiotic in the body, often described as “what the body does to a drug” (Buxton 2023; Glassman and Muzykantov 2019). The pharmacologic and toxicologic effect(s) of a drug are generally dependent on the concentration of the drug at its target(s) within the organism (Slitt 2019). Therefore, pharmacokinetics is integral to the study of safety pharmacology and toxicology. The pharmacokinetic profile of a drug is broadly divided into four categories including absorption (entry into the body), distribution (movement and storage in the body’s tissue), metabolism (biotransformation), and excretion (via renal, fecal, or pulmonary excretion). These factors, often abbreviated “ADME”, ultimately determine the concentration of a drug in different organs including at its target(s). Pharmacodynamics is the study of how the drug interacts with site(s) of action, often described as “what the drug does to the body.” As such, regulatory agencies increasingly focus on the interplay between the pharmacokinetic profile and the pharmacodynamic profile when assessing drug safety. This relationship is coined the pharmacokinetic/pharmacodynamic (PK/PD) relationship.