Fate of Medicines in the Body: Absorption, Distribution, Metabolism and Excretion
10 minute read
What you will learn
- Describe absorption and the factors that affect it
- Explain distribution and protein binding
- Explain how drugs act on receptors, and define agonist and antagonist
- Describe metabolism and the first-pass effect
- Describe how drugs are excreted
- Calculate the amount of drug left after a number of half-lives, and bioavailability
Key points
- The fate of a medicine is described by absorption, distribution, metabolism and excretion (ADME).
- Absorption is the movement of the drug from the site of giving into the blood.
- Distribution is the spread of the drug from the blood to the tissues.
- Drugs act by binding to receptors. An agonist activates a receptor, and an antagonist blocks it.
- Metabolism, mainly in the liver, usually turns drugs into forms that are easier to remove.
- Excretion removes drugs and their metabolites, mainly through the kidneys.
- Half-life is the time for the amount of drug in the blood to fall by half.
The journey of a medicine
After a medicine is taken, it goes through four steps, often called ADME:
Absorption → Distribution → Metabolism → Excretion
The study of these steps is called pharmacokinetics. The curriculum also includes receptor affinity, which links the drug to its effect.
1. Absorption
Absorption is the movement of the drug from the place where it is given into the blood.
| Route | Absorption |
|---|---|
| Oral (swallowed) | Through the stomach and mainly the small intestine. Slower, and some drug is lost |
| Injection into a vein (intravenous) | None needed. The drug is in the blood at once |
| Injection into muscle or under the skin | Fairly quick, depending on the blood supply |
| Rectal | Partly avoids the liver, useful if the patient is vomiting |
| Under the tongue (sublingual) | Fast, direct into the blood, avoids the liver |
| Skin (transdermal) | Slow and steady through patches |
| Inhaled | Fast in the lungs |
Factors that affect oral absorption
- How well the drug dissolves and its form: solutions are absorbed faster than tablets.
- Acid or alkali conditions in the stomach and gut.
- Food: it can slow or reduce absorption of some drugs, and increase that of others.
- Gut movement: diarrhoea reduces absorption, and slow emptying delays it.
- Other drugs, such as antacids binding to tetracyclines.
- Disease of the gut.
First-pass effect and bioavailability
Blood from the gut passes through the liver first. The liver may break down much of the drug before it reaches the rest of the body. This is the first-pass effect.
Bioavailability is the percentage of the dose that reaches the blood in an active form.
bioavailability (%) = amount reaching the blood ÷ dose given × 100
Example. A 100 mg oral dose gives 60 mg in the blood.
- Bioavailability = 60 ÷ 100 × 100 = 60%
An intravenous dose has a bioavailability of 100%.
2. Distribution
Distribution is the spread of the drug from the blood into the body. It depends on:
- blood flow: organs with a good supply, such as the heart, liver, kidney and brain, receive drug first;
- how easily the drug passes through membranes, which depends on its size and whether it dissolves in fat or water;
- binding to blood proteins such as albumin. A drug bound to protein is inactive and cannot leave the blood. Only the free drug acts. A drug can be pushed off the protein by another drug, which can raise the free level and cause toxicity;
- barriers: the blood-brain barrier protects the brain, and the placenta lets many drugs reach the unborn baby. Many drugs also pass into breast milk, so the pharmacist must check these in pregnancy and breast-feeding.
3. Receptor affinity
Most drugs act by binding to receptors, which are special molecules on or in cells. This is like a key fitting a lock.
| Term | Meaning |
|---|---|
| Receptor | A cell molecule to which a drug or natural chemical binds |
| Affinity | How strongly a drug is attracted to and binds with its receptor |
| Efficacy | The ability of the drug, once bound, to produce an effect |
| Agonist | A drug that binds and activates the receptor, producing an effect |
| Antagonist | A drug that binds and blocks the receptor without activating it |
Examples. Salbutamol is an agonist at receptors in the airways, so the airways open. A beta-blocker is an antagonist at heart receptors and slows the heart.
Some drugs do not use receptors. For example, antacids neutralise acid, and some antibiotics attack parts of germs.
4. Metabolism
Metabolism is the chemical change of a drug in the body, mainly by enzymes in the liver. It usually makes the drug more water-soluble and less active, so that the kidneys can remove it. The products are metabolites.
- Some drugs are changed into active metabolites. A prodrug is inactive until metabolised.
- Enzyme inducers (for example rifampicin and some antiepileptics) speed up metabolism, so other drugs may be weaker.
- Enzyme inhibitors (for example some antifungals and erythromycin) slow down metabolism, so other drugs may be stronger and more toxic.
- Metabolism is slower in newborns, the elderly and people with liver disease, so doses may need to be changed.
5. Excretion
Excretion is the removal of the drug and its metabolites from the body.
| Route | Notes |
|---|---|
| Kidneys (urine) | The main route. Poor kidney function means the drug builds up |
| Bile and faeces | Some drugs pass into the bile, and may be reabsorbed |
| Lungs | Gases and volatile drugs, such as anaesthetics |
| Sweat, saliva, tears | Small amounts |
| Breast milk | Small amounts, but important for the infant |
Half-life
The half-life (t½) is the time taken for the amount of drug in the blood to fall by half.
Example. A drug has a half-life of 4 hours. 100 mg is in the blood.
| Time | Number of half-lives | Amount left |
|---|---|---|
| 0 h | 0 | 100 mg |
| 4 h | 1 | 50 mg |
| 8 h | 2 | 25 mg |
| 12 h | 3 | 12.5 mg |
A drug with a long half-life can be taken less often, and a drug with a short half-life may need frequent dosing. After about 5 half-lives, a drug is almost completely removed.
Why this matters
- The route and form decide how fast the drug acts.
- Food, other drugs and disease change the dose needed.
- Kidney or liver disease, age and pregnancy affect safe doses, so a pharmacist checks these.
- The half-life decides how often a medicine is given.
Exam focus
- Define each of A, D, M and E, and give two factors affecting each.
- Define agonist, antagonist, affinity, half-life and bioavailability.
- Calculate the drug remaining after a number of half-lives.
- Common mistake: thinking that all drugs are removed by the kidney. Many are first changed by the liver.
Quick check
Test yourself before you move on. Pick an answer to see the explanation.
1.Absorption is:
2.The main organ of drug metabolism is the:
3.A drug that binds to a receptor and blocks its action is called:
4.A drug has a half-life of 4 hours. If 100 mg is in the blood now, how much is left after 8 hours, ignoring any new doses?
5.A 100 mg oral dose gives 60 mg of drug reaching the blood. What is its bioavailability?