Pharmacokinetics: absorption and distribution !

What the body does to a drug: how it gets in, how much reaches the blood and where it goes before it is broken down or removed.

Updated 2026-11-01

Pharmacokinetics follows a drug through the body in four stages: absorption, distribution, metabolism and elimination. This page covers the first two. They decide how quickly a drug starts to act, how much of each dose actually reaches the circulation, and which tissues it can reach.

Routes and absorption

Every route trades speed and control against convenience. Intravenous drugs skip absorption entirely. Oral drugs must dissolve, survive stomach acid and cross the intestinal wall; food, gut motility, formulation and pH all change how much gets through and how fast.

Enteral: oral, sublingual, rectal
Parenteral: intravenous, intramuscular, subcutaneous
Others: inhaled, transdermal, topical, intrathecal
Some drugs are not absorbed from the gut at all and are only given by injection, as with gentamicin.

Bioavailability and the first-pass effect

Blood from the intestine goes to the liver through the portal vein before it reaches the heart. Enzymes in the gut wall and the liver can remove part of an oral dose on this first pass, which is why some drugs need much larger oral than intravenous doses, or cannot be given orally. Grapefruit juice blocks intestinal CYP3A4, so less of some drugs (such as simvastatin) is broken down on the way in and their blood levels rise.

Distribution and volume of distribution

After absorption the drug spreads with the blood. Organs with high blood flow receive it first; fat and inactive tissues later. The apparent volume of distribution (Vd) links dose and concentration: drugs that stay in plasma have a small Vd, drugs that pack into tissues have a very large one. The Vd decides how big a loading dose has to be.

Protein binding

Many drugs ride on plasma proteins, mostly albumin (acidic drugs) or alpha-1 acid glycoprotein (basic drugs). Bound drug is a reservoir: it cannot reach receptors or be filtered by the kidney. When albumin is low (liver disease, malnutrition, nephrotic syndrome) or another drug competes for the same site, the free fraction rises. For phenytoin, the label recommends measuring the unbound level in hypoalbuminaemia or kidney and liver disease, because the total level can mislead.

Barriers

The blood–brain barrier and the placenta let lipid-soluble drugs through more easily than charged or very large molecules. Efflux pumps such as P-glycoprotein also push some drugs back out (see drug transporters).

Test yourself

Think of the answer, then tap the question to see it.

Why is an intravenous dose described as fully bioavailable?

Because it enters the systemic circulation directly, with no absorption step and no first-pass loss in the gut wall or liver.

What does a very large volume of distribution suggest about a drug?

That most of the drug is in tissues rather than in plasma, so its plasma concentration is low relative to the amount in the body.

Why can a normal total phenytoin level hide toxicity in a patient with low albumin?

Less phenytoin is bound, so the free (active) fraction is higher than the total level suggests; the unbound level is the useful one.

How does grapefruit juice raise the blood level of some oral drugs?

It blocks CYP3A4 in the intestinal wall, so less of the drug is broken down during absorption (first pass).

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Example drugs

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - EXTENDED PHENYTOIN SODIUM- phenytoin sodium capsule (DailyMed (U.S. National Library of Medicine), 2026); Grapefruit Juice and Some Drugs Don't Mix (U.S. Food and Drug Administration, 2026); DailyMed - WARFARIN SODIUM tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - GENTAMICIN SULFATE injection, solution (DailyMed (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.