Pharmacokinetics describes what the body does to a drug after it is given. The four main stages are absorption, distribution, metabolism, and excretion, often shortened to ADME. These processes determine how quickly a drug starts working, how strong its effects are, and how long it stays in the body.
Understanding ADME helps students connect drug dosing to real clinical outcomes such as efficacy, toxicity, and drug interactions.
After administration, a drug must enter the bloodstream, move into tissues, be chemically changed, and then leave the body. Absorption depends on route, membrane transport, and blood flow, while distribution depends on perfusion, protein binding, and tissue barriers. Metabolism occurs mainly in the liver and often makes drugs easier to eliminate, though some drugs are activated there.
Excretion occurs mainly through the kidneys, and changes in liver or kidney function can strongly alter drug levels.
Understanding Pharmacokinetics
A drug taken by mouth faces several obstacles before it can produce an effect. It must dissolve in stomach or intestinal fluid, cross the gut wall, then survive passage through the liver. Some of the dose can be broken down before reaching the general circulation.
This is called first pass metabolism. It explains why a tablet dose may be much larger than a dose given directly into a vein. Food can slow stomach emptying or bind certain medicines.
For example, calcium in dairy products can reduce absorption of some antibiotics. Vomiting, diarrhoea, gut disease, and poor blood flow can make oral drug uptake less reliable.
Once in blood, a drug does not spread evenly through the body. Blood flow delivers it quickly to highly perfused organs such as the brain, heart, liver, and kidneys. Fat tissue, muscle, bone, and other tissues may take up a drug more slowly.
Drugs that dissolve well in fat can collect in fatty tissue and remain there after blood levels fall. Some drugs bind to blood proteins, especially albumin.
Only the unbound portion can usually cross membranes, reach a target, or be removed by the kidneys. Low albumin levels, seen in severe illness or malnutrition, can increase the active unbound fraction of certain drugs.
The liver changes many drugs using enzymes. These enzymes may make a drug inactive, create an active product, or sometimes form a harmful product. Enzyme activity differs between people because of genes, age, liver disease, diet, and other medicines.
A medicine that speeds up liver enzymes can lower the level of another drug. A medicine that blocks those enzymes can raise the level and increase side effects. Grapefruit can block an intestinal enzyme that normally breaks down several medicines.
This can cause unexpectedly high drug concentrations. Students should distinguish metabolism from elimination. A drug can be metabolised into a product that still needs to leave the body.
Kidneys remove drugs and their metabolites through urine. They filter unbound drug from blood, sometimes actively secrete drug into kidney tubules, and may reabsorb some drug back into blood. Urine acidity can influence reabsorption for a few drugs because it changes whether molecules carry an electrical charge.
Reduced kidney function slows removal, so standard doses may accumulate over repeated use. This is why clinicians use kidney blood tests when choosing doses for many antibiotics, pain medicines, and diabetes drugs.
A drug level often approaches a stable average after several half lives. Missing doses, taking extra doses, or changing the timing can disturb that pattern, especially for drugs with narrow safety margins such as warfarin, lithium, and digoxin.
Key Facts
- Bioavailability: F = amount reaching systemic circulation / administered dose
- Volume of distribution: Vd = amount of drug in body / plasma drug concentration
- Clearance: CL = rate of elimination / plasma drug concentration
- Half-life for first-order elimination: t1/2 = 0.693 x Vd / CL
- Loading dose: Loading dose = target concentration x Vd / F
- Maintenance dose rate: Maintenance dose rate = CL x target concentration / F
Vocabulary
- Bioavailability
- Bioavailability is the fraction of an administered dose that reaches the systemic circulation unchanged.
- First-pass metabolism
- First-pass metabolism is drug metabolism in the gut wall or liver before the drug reaches the systemic circulation.
- Volume of distribution
- Volume of distribution is an apparent volume that relates the amount of drug in the body to its plasma concentration.
- Clearance
- Clearance is the volume of plasma from which a drug is completely removed per unit time.
- Half-life
- Half-life is the time required for the plasma concentration of a drug to fall to half of its current value.
Common Mistakes to Avoid
- Assuming oral dose equals systemic dose, which is wrong because incomplete absorption and first-pass metabolism can reduce the amount reaching circulation.
- Confusing volume of distribution with a real anatomical volume, which is wrong because Vd is a calculated value that reflects how widely a drug leaves the plasma.
- Thinking metabolism always inactivates drugs, which is wrong because some drugs are converted into active metabolites or activated from prodrugs.
- Assuming a long half-life always means poor kidney excretion, which is wrong because half-life depends on both clearance and volume of distribution.
Practice Questions
- 1 A drug is given orally at 200 mg, and 120 mg reaches the systemic circulation unchanged. What is the bioavailability F?
- 2 A drug has Vd = 40 L and CL = 5 L/hour. Calculate its half-life using t1/2 = 0.693 x Vd / CL.
- 3 A patient with severe liver disease is given a drug that normally undergoes extensive first-pass metabolism. Explain how this could change oral bioavailability and why the dose might need adjustment.