Pharmacokinetics
What the body does to a drug — absorption, distribution, metabolism, and excretion — and the numbers that govern dosing.
Pharmacokinetics is the study of what the body does to a drug: how the drug moves into, through, and out of the body over time. It is conventionally summarized as ADME — absorption, distribution, metabolism, and excretion — and it is paired with pharmacodynamics, the study of what the drug does to the body. Together they determine the dose, the route, and the schedule of every medicine.
Absorption describes how a drug enters the bloodstream. The route matters: intravenous drugs enter directly, oral drugs must survive the gut and pass through the liver, and inhaled or transdermal drugs cross other barriers. Bioavailability is the fraction of a dose that reaches the systemic circulation; for oral drugs it is reduced by incomplete absorption and by first-pass metabolism in the liver, which can be so extensive that some drugs are not given orally at all. Drug chemistry drives absorption: weak acids and weak bases are absorbed differently depending on the pH of the compartment, a direct application of acid–base chemistry.
Distribution is the reversible movement of drug from blood into tissues. Many drugs bind plasma proteins such as albumin; only the unbound fraction is pharmacologically active. The apparent volume of distribution (Vd) relates the dose to the plasma concentration and is a mathematical convenience, not a real space: a large Vd means the drug leaves the plasma and accumulates in tissues. The blood–brain barrier limits distribution into the central nervous system, and only lipophilic drugs cross it readily — a major constraint in neuropharmacology.
Metabolism, mostly in the liver, transforms drugs into more water-soluble products that can be excreted. The cytochrome P450 enzyme family — especially CYP3A4, CYP2D6, and CYP2C9 — performs most phase I oxidations, and conjugation reactions (phase II) attach groups that enhance excretion. Metabolism creates enormous variability: genetic polymorphisms (such as CYP2D6 poor metabolizers) change effective doses between individuals, and drug–drug interactions arise when one drug induces or inhibits another's metabolizing enzyme — grapefruit juice inhibits intestinal CYP3A4, raising the levels of many drugs. Some drugs are administered as prodrugs that only become active after metabolic conversion.
Excretion is dominated by the kidneys: glomerular filtration, tubular secretion, and pH-dependent reabsorption remove drug and metabolites, with biliary excretion as a secondary route. The key derived quantities are clearance (the volume of plasma cleared per unit time), half-life (the time for plasma concentration to halve), and the steady state reached after roughly four to five half-lives of regular dosing — the reason some drugs need a loading dose. The therapeutic window is the concentration range between the minimum effective and the toxic concentrations; drugs with narrow windows (digoxin, warfarin, lithium) require therapeutic drug monitoring. Renal or hepatic impairment shrinks clearance and forces dose adjustment. Pharmacokinetic models, from simple one-compartment equations to population models, turn these concepts into the dosing regimens that clinicians actually use. This article is an educational reference and is not medical advice.