Pharmacokinetics

Pharmacokinetics (PK) describes what the body does to a substance from the moment it enters until the last trace is gone. It maps four sequential processes — absorption, distribution, metabolism, and excretion, collectively abbreviated ADME — and summarises them as measurable parameters: Tmax (time to peak concentration), Cmax (peak concentration), half-life, clearance, and volume of distribution.

PK is the counterpart to pharmacodynamics, which describes what a substance does to the body. Together they give a complete picture: pharmacokinetics explains the timing and intensity of exposure; pharmacodynamics explains what that exposure triggers at receptors and in tissues.

For many substances indexed here, human PK data is sparse or absent. Parameters may come from animal studies, small clinical samples, or conditions that don't reflect typical use — a limit this encyclopedia notes wherever it applies.

How it works · its role

Absorption is the first step: a substance crosses a biological barrier to enter the bloodstream. The route of administration determines how fast and how completely this happens. Inhaled compounds reach the blood in seconds; oral compounds pass through the gut wall and, crucially, the liver before reaching circulation, losing some fraction to what is called first-pass metabolism. Bioavailability — the percentage that arrives intact — captures this difference.

Distribution follows: the compound spreads from blood into tissues. Lipophilic (fat-soluble) substances cross the blood–brain barrier more readily and tend to accumulate in fatty tissue, reflected in a large volume of distribution. Protein binding in plasma can keep a fraction of the drug temporarily sequestered.

Metabolism, primarily in the liver via Cytochrome P450, converts the substance into metabolites — some inactive, some pharmacologically active in their own right. Excretion, mainly through the kidneys, clears those products from the body. Half-life — the time for plasma concentration to halve — is the single most practical summary of how long a substance persists.

Relevance to substances & effects

PK parameters map directly onto what a person experiences. Half-life shapes duration: a compound with a long half-life produces a sustained effect; one with a short half-life produces a brief, sharp one. Tmax — the time to peak plasma concentration — approximates when effects will be felt most strongly, and helps explain why the same compound can behave noticeably differently depending on how it is taken.

Route of administration creates large PK differences for the same molecule. Oral dosing involves absorption delays and first-pass metabolism; inhalation and insufflation bypass both, producing faster onset and a different concentration profile even at comparable doses.

Active metabolites add another layer. Psilocybin is itself pharmacologically inert; the body rapidly converts it to psilocin, the compound responsible for its effects. Codeine is partially converted to morphine by the CYP2D6 enzyme, so its effective potency varies considerably with an individual's metabolic phenotype.

When a CYP enzyme is inhibited by a co-administered substance, a drug can accumulate to higher plasma concentrations than anticipated. This is the mechanistic basis for a large class of drug–drug interactions — and the reason PK context sits alongside pharmacodynamic data throughout the combination-risk information on this site.