Plasma

Plasma is the liquid fraction of blood — the pale yellow fluid that suspends red cells, white cells, and platelets. It makes up roughly 55% of total blood volume and carries water, salts, proteins, hormones, and dissolved substances, including every drug that has entered the bloodstream.

When pharmacologists speak of drug concentration in the body, they almost always mean plasma concentration. It is the standard measurement because plasma is reliably sampled, reflects what the circulatory system is delivering to tissues, and changes predictably as a drug is absorbed, distributed, metabolised, and cleared.

How it works · its role

Once a substance reaches the bloodstream — whether by swallowing, injecting, inhaling, or absorbing through skin — it circulates dissolved in plasma. Its concentration rises as absorption continues, peaks, then falls as the body metabolises and eliminates it. That arc, traced over time, is the concentration–time curve: the empirical backbone of most pharmacokinetic data.

Plasma is not a passive carrier. Many drugs bind to plasma proteins, particularly albumin. Only the unbound fraction — the free drug — can cross cell membranes and reach its target. High protein binding means more drug is temporarily sequestered in plasma, which extends circulation time and can shape interactions when two drugs compete for the same binding sites.

Relevance to substances & effects

Most pharmacokinetic measures that appear across this encyclopedia — half-life, Cmax (peak concentration), Tmax (time to peak), and bioavailability — are defined relative to plasma concentration.

Half-life determines how long effects last and how quickly a substance clears the body. It also governs accumulation: a compound with a long half-life builds up in plasma with repeated doses, intensifying effects beyond what a single dose would suggest. This matters across many classes, from long-acting benzodiazepines to methadone.

Route of administration directly shapes the plasma curve. Intravenous injection delivers a substance into the bloodstream immediately, producing a sharp peak. Oral administration adds time for gut absorption and first-pass liver metabolism, which can substantially reduce how much of the original compound reaches systemic circulation. Inhaled and sublingual routes sit between these extremes, bypassing first-pass metabolism while still absorbing more gradually than injection.

Individual differences — body composition, liver enzyme activity, kidney function, age — mean that the same oral dose produces meaningfully different plasma concentrations in different people. This variation underlies much of the unpredictability in how substances affect individuals, and is why population-average pharmacokinetic figures are a guide, not a guarantee.