Pharmacokinetics is the branch of pharmacology concerned with the movement of a drug through the body over time. It is commonly summarised by the processes of absorption, distribution, metabolism and excretion, collectively abbreviated as ADME. Pharmacokinetics examines how drug concentrations change in plasma, tissues and other biological compartments after administration and how those concentration-time relationships influence dosing. Important concepts include bioavailability, volume of distribution, clearance, half-life, area under the concentration-time curve and steady-state concentration. Pharmacokinetics is distinct from pharmacodynamics, which focuses on the biological effects produced by a drug rather than its concentration-time behaviour.
Absorption describes the movement of a drug from its administration site into systemic circulation. Intravenous administration delivers drug directly into the circulation and therefore has complete systemic bioavailability, while oral administration requires passage through the gastrointestinal tract and can be affected by dissolution, intestinal absorption, transporters, gastric emptying and first-pass metabolism. Other routes, including subcutaneous, intramuscular, inhaled, transdermal and buccal administration, have different absorption characteristics. Lipid solubility, molecular size, ionisation, formulation and local blood flow can all influence absorption. The rate and extent of absorption are separate concepts: two formulations can ultimately deliver similar amounts systemically while reaching peak concentrations at different speeds.
Distribution describes the reversible movement of drug between the bloodstream and tissues. It is influenced by blood flow, tissue permeability, lipid solubility, plasma-protein binding and tissue binding. Highly perfused organs can receive drug rapidly, whereas poorly perfused tissues may equilibrate more slowly. Some drugs remain largely within the vascular compartment, while others distribute extensively into tissues and can produce a large apparent volume of distribution. The blood-brain barrier restricts entry of many compounds into the central nervous system, while placental transfer can expose a developing fetus to drugs taken by a pregnant person. Distribution is dynamic and can change as plasma concentrations fall and drug redistributes between compartments.
Metabolism, often called biotransformation, chemically modifies drugs and other substances, primarily through enzymes in the liver but also through the intestine, kidneys, lungs and other tissues. Phase I reactions can include oxidation, reduction and hydrolysis, while Phase II reactions commonly attach polar groups to facilitate elimination, although these categories do not encompass every metabolic pathway. Cytochrome P450 enzymes are important for the metabolism of many drugs and can be inhibited or induced by other substances. Metabolism can inactivate a drug, activate a prodrug or generate an active or toxic metabolite. First-pass metabolism can substantially reduce the systemic availability of some orally administered medicines before they reach the general circulation.
Excretion removes drugs and metabolites from the body, with the kidneys playing a major role for many compounds. Renal elimination can involve glomerular filtration, active tubular secretion and tubular reabsorption. Biliary excretion can move drugs or metabolites into the intestine, where some substances may be reabsorbed through enterohepatic circulation. Other routes include exhalation, sweat, saliva and breast milk, although their quantitative importance varies greatly. Kidney and liver function therefore have major implications for drug exposure. Reduced clearance can increase concentrations and prolong drug action, sometimes requiring dose adjustment or altered dosing intervals to avoid accumulation and toxicity.
Pharmacokinetic parameters provide quantitative descriptions of drug handling. Clearance represents the efficiency with which drug is removed from a defined volume of plasma per unit time, while volume of distribution is an apparent parameter relating the amount of drug in the body to its measured plasma concentration. Elimination half-life is the time required for plasma concentration to fall by half under specified pharmacokinetic conditions and depends on clearance and volume of distribution. Area under the concentration-time curve is related to systemic exposure. Bioavailability describes the fraction of an administered dose reaching systemic circulation in an unchanged form, and is especially relevant when comparing non-intravenous routes with intravenous administration.
Pharmacokinetic models simplify complex biological processes. A one-compartment model treats the body as a single kinetically homogeneous compartment, while multi-compartment models represent distribution into multiple kinetically distinct spaces. Many drugs approximate first-order elimination over therapeutic concentrations, meaning a constant fraction is eliminated per unit time, but some drugs exhibit capacity-limited or zero-order behaviour over relevant concentration ranges. Repeated dosing produces accumulation until input and elimination reach a dynamic equilibrium. At steady state, average drug exposure is determined by dosing rate and clearance, while the time required to approach steady state is related to the drug's effective half-life. Loading doses can be used when rapid attainment of therapeutic concentrations is important.
Pharmacokinetics is essential for selecting dose, dosing interval and route of administration and for understanding why patients may require different regimens. Age, body size, organ function, pregnancy, genetics, diet and interacting medicines can alter absorption, distribution, metabolism or elimination. Therapeutic drug monitoring can measure concentrations for medicines with relatively narrow therapeutic windows or substantial variability in exposure, although concentration targets must be interpreted in clinical context.
Pharmacokinetics does not by itself establish whether a concentration is therapeutically effective because pharmacodynamic sensitivity can vary independently. A common misconception is that a drug's half-life directly equals the duration of clinical effect; pharmacological effects can persist longer or shorter than plasma concentrations depending on receptor binding, active metabolites, irreversible target interactions and downstream biological changes.
