BMS 123 · Common Core (Tronc commun)Section 2.1 · Drug distribution
Section 6 of 27
Distribution and the volume of distribution
Explain what drug distribution is, why it is not uniform, and how the apparent volume of distribution is calculated from a dose and a plasma concentration.
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Why this matters
Distribution decides which tissues see a drug and how much of the dose stays in the blood. If you cannot read a volume of distribution, you cannot judge whether a drug will act quickly or slowly, whether it will accumulate, or whether an overdose can be removed by dialysis. The same dose can behave very differently in two patients because their tissues take the drug up differently.
What you need to know first
You need the idea from Unit 1 that absorption carries a drug from its site of administration into the bloodstream, and you should be comfortable dividing one number by another. No anatomy beyond the everyday words blood, tissue and organ is assumed.
Words to know (4)
Distribution
The reversible movement of a drug from the bloodstream into the tissues and organs, including its site of action. A sleeping drug entering the brain after an intravenous injection is distributing.
Disposition
Everything the body does to a drug after it reaches the blood: distribution plus elimination. A falling plasma concentration after a dose is caused by disposition.
Apparent volume of distribution (Vd)
The volume the dose would need to occupy to give the measured plasma concentration, calculated as dose divided by concentration. A 500 mg dose giving 100 mg/L has a Vd of 5 L.
Total body water
All the water in the body: about 42 litres in a 70 kg adult, used as the reference for reading Vd. Alcohol distributes through total body water and has a Vd near 42 L.
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In one sentence Drug distribution is the reversible movement of drug from the bloodstream into the tissues and organs, including the site where it acts.
Distribution carries drug from blood into tissues
Once a drug has been absorbed into the bloodstream, it does not stay there. Distribution is the process by which it moves from the blood into the other fluids, tissues and organs of the body, including the tissue where it will produce its effect. The process is reversible: drug moves back and forth between blood and tissue, so a drug that has entered fat may later return to the circulation, be redistributed to another organ, and finally be eliminated.
For example
An intravenous anaesthetic is absorbed directly into the blood, then distributed within seconds to the well-perfused brain, where it produces sleep before being redistributed to other tissues.
Think of it like
Distribution is like ink dropped into a sponge that is already soaked in water: it spreads from the wet channels into the solid material and can seep back again. The image has a limit, because a real drug binds to proteins and tissues and does not spread evenly like ink.
Pause and check yourself
In which direction does distribution move a drug, and is the movement reversible?
Show the answer
From the bloodstream into the tissues and organs, including the site of action. Yes, it is reversible: drug moves back into the blood for redistribution and elimination.
Read detailed explanations
Why the body behaves like more than one compartment
If the body were a single well-stirred tank, a drug injected into the vein would mix instantly and the plasma concentration would fall in a smooth curve as elimination proceeded. In reality, the curve often falls in two phases. The first, fast phase is distribution: the drug leaves the blood for the well-perfused organs — brain, heart, liver, kidneys — and the plasma level drops quickly without any drug having left the body. The second, slower phase is elimination, in which metabolism and excretion remove drug and the level falls more gently. The anaesthetic thiopental shows the pattern clearly. It is lipophilic, so it enters the brain within seconds and produces sleep, but the plasma level then falls partly because the drug redistributes into muscle and fat. When fat later releases it slowly, a second dose can produce unexpectedly deep and prolonged effects. This is why a measured Vd depends on when the blood sample was taken: a sample drawn during the fast distribution phase gives a smaller apparent volume than one drawn after equilibration. Always ask when the sample was taken before trusting the number.
What a volume of distribution does and does not tell you
The volume of distribution is a bridge between a measured concentration and the amount of drug in the body. If the plasma level is known and the Vd is known, the total amount present can be estimated, which is why the figure reappears in discussions of overdose and of loading a patient quickly. It also links to elimination: total clearance, the volume of blood cleared of drug per unit time, is related to both Vd and half-life by the expression clearance equals 0.693 times Vd divided by half-life. A drug with a large Vd therefore needs a long time to be cleared at any given clearance, which is one reason widely distributed drugs act for longer. But Vd says nothing about how well a drug works, how toxic it is, or where exactly it acts. A large volume may reflect harmless storage in fat or dangerous binding in the heart and brain, and the same number can arise from very different mechanisms. It is also measured in a defined way: the dose used should be the amount that reached the circulation. For an oral drug, some of the dose is lost before it arrives, so the intravenous route is preferred when an accurate Vd is wanted. Treat the figure as a compass bearing, not as a map.
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Drug distribution: blood to tissues
After absorption the drug leaves the bloodstream and enters the tissues, reaching its site of action and its storage sites, then returns to the blood to be eliminated.
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01 / 5Distribution
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Distribution
The process by which a drug moves from the bloodstream into the tissues and organs of the body, including the tissue where it produces its effect. It is reversible, so the drug returns to the blood for redistribution and eventual elimination.
Schematic, not to scale. Blood flow, tissue size and the drug’s own solubility all shape the picture, so the same drug can be widely distributed in one patient and narrowly in another.
Key points to remember
✓Distribution is the reversible movement of drug from blood into tissues, including the site of action.
✓Disposition equals distribution plus elimination, and both lower the plasma concentration.
✓Distribution is not uniform: blood flow, tissue size and the drug’s chemistry decide where it goes.
✓A 70 kg adult has about 42 L of water: 28 L intracellular and 14 L extracellular, which is 10 L interstitial plus 4 L plasma.
✓The apparent volume of distribution is dose divided by plasma concentration, and it is a calculated volume, not a real space.
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Worked example
Calculating and comparing two volumes of distribution. A patient receives 500 mg of paracetamol and later 500 mg of amoxicillin. The measured plasma concentrations are 100 mg/L for paracetamol and 80 mg/L for amoxicillin. Calculate the apparent volume of distribution of each drug and say what the two figures suggest.
Write the formula for both drugs: Vd = dose administered ÷ plasma concentration.
Paracetamol: Vd = 500 mg ÷ 100 mg/L = 5 L. A small apparent volume, close to the plasma and extracellular fluid volumes.
Amoxicillin: Vd = 500 mg ÷ 80 mg/L = 6.25 L. Also a small apparent volume, on the same scale as paracetamol.
Compare: amoxicillin has a slightly larger Vd because its plasma concentration is lower for the same dose. A larger volume means the drug is spread into more fluid or tissue.
Interpret cautiously: a larger Vd usually goes with a longer half-life and a longer duration of action, so the drug is cleared more slowly and repeated doses may accumulate.
Both drugs have small apparent volumes, so both stay largely in plasma and extracellular fluid. The comparison only makes sense when the dose, the timing of the blood sample and the assay are the same; the number describes the whole body, not one organ.
Common misconception
Beginners often picture the volume of distribution as the real space the drug occupies in the body, like water filling a tank. It is not: it is a calculated, apparent volume that can even exceed the whole body when the drug is concentrated in tissue.
Check your reasoning
A colleague says that because a drug has a Vd of 100 L, the patient must have 100 litres of fluid somewhere. How would you correct this in one or two sentences?
Reveal an answer
The volume is apparent, not anatomical. It is the volume the dose would occupy if the body were a single uniform water compartment; a value above total body water simply means that much of the drug is bound or stored in tissues, leaving a low plasma concentration.
Where this comes from
GENERAL PHARMACOLOGY II lecture notes (PHM112), St. Louis University Institute, Douala · Lecture 2: Drug Distribution, sections 1.1–1.3.1 and 1.4
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About this course and its sources
Bilingual lessons organised from the supplied BMS 123 General Pharmacology II lecture notes (Principles of Pharmacokinetics and Principles of Pharmacodynamics). Diagrams are original educational schematics; pharmacology, nursing and French-language review are pending.