What is pharmacogenetics? Same dose, different effect

Reviewed by Dr. Daniel Wallerstorfer, molecular biologist and founder of Novogenia · Updated: 13 October 2026 · Reading time: 9 min

In short

Pharmacogenetics studies how inherited gene variants influence the effect and tolerability of drugs. Most of the time, it is about enzymes that break down drugs or activate them in the first place. Depending on how well they work, there are five metabolizer types – from poor to ultrarapid. With prodrugs such as codeine, the logic flips: a fast enzyme produces more active drug. In the UK Biobank, 99.5% of participants carried variants that could cause an atypical response to at least one drug. A result is a decision aid; decisions about medication are made by the treating physician.

A cough medicine with an unexpected effect

A team of physicians in Geneva described a man with pneumonia in both lungs who was given small doses of codeine for his cough. He then developed life-threatening opioid poisoning. The team found the cause in his genes: he carried three or more functional copies of the CYP2D6 gene. CYP2D6 converts codeine into morphine – and in his body, that conversion was running at full speed. Two other factors added to it: other drugs slowed down a second metabolic enzyme (CYP3A4), and his kidney function was temporarily reduced (Gasche et al., New England Journal of Medicine, 2004).

This single case shows what pharmacogenetics is about: genes help determine what a drug does in the body – together with co-medication, organ function and much more. And it carries the good news: today, such differences can be identified in the lab before a prescription is written.

Same dose, different effect

Pharmacogenetics studies how inherited gene variants influence the effect and tolerability of drugs. This refers to variants a person inherited from their mother and father, which do not change over a lifetime – not the changes within a tumor, which are also tested in oncology.

You know the principle from coffee: about 95% of caffeine is broken down by a single liver enzyme, built from the blueprint of the CYP1A2 gene. If it works fast, the caffeine is soon cleared; if it works slowly, the caffeine stays in the body much longer (Caffeine and the CYP1A2 gene). Drugs follow the same principle – only here, it is about efficacy and side effects.

Genes are one factor among many. Age, weight, kidney and liver function, co-medication and whether a drug is taken regularly all play a part too. Pharmacogenetics adds a piece that has mostly been missing from this picture: the body’s inborn metabolic equipment.

The bathtub: five metabolizer types

Picture the drug in the blood as water in a bathtub. The dose is the faucet, and the enzyme that breaks the drug down is the drain. In most people, inflow and outflow are balanced, and the water level stays in the desired range. If the drain is narrowed, the level rises – the tub threatens to overflow, and side effects become more likely. If the drain is wide open, the tub stays almost empty, and the drug barely works.

Depending on how well the two gene copies work, five types are distinguished. The terms were standardized by the CPIC consortium: in a multi-round consensus process with 58 experts from clinical care, research and the lab, 90% ultimately agreed on the uniform terms (Caudle et al., Genetics in Medicine, 2017).

Type	What happens in the body	The bathtub image
Poor metabolizer (PM)	Neither gene copy works, or they barely work; the enzyme is largely missing.	Drain almost closed
Intermediate metabolizer (IM)	Enzyme activity is reduced, for example because one gene copy does not work.	Drain narrowed
Normal metabolizer (NM)	The enzyme works as expected; guidelines usually recommend the standard dose here.	Inflow and outflow in balance
Rapid metabolizer (RM)	Increased activity; CPIC uses this category mainly for CYP2C19.	Drain somewhat wider
Ultrarapid metabolizer (UM)	Markedly increased activity, in CYP2D6 for example due to extra gene copies.	Drain wide open

Everyone carries two copies of each gene, one from the mother and one from the father. Only the combination of both copies determines the type: one working copy and one non-working copy, for example, often add up to an intermediate metabolizer. How the lab and the guideline derive the type from the gene copies is explained in Understanding and communicating results.

The image describes a tendency, not destiny. Whether slow breakdown actually leads to too much effect also depends on the drug, the dose and other metabolic pathways.

Prodrugs: when the logic flips

Some drugs enter the body as a precursor and only become the actual active drug through an enzyme. With these prodrugs, the enzyme is not the drain but the faucet: it fills the tub with the active substance. A poor metabolizer then produces too little active drug, and an ultrarapid metabolizer too much.

Codeine is the classic example: CYP2D6 turns it into morphine. The CPIC guideline therefore advises against codeine in CYP2D6 ultrarapid metabolizers because of the potential for serious toxicity – and in poor metabolizers as well, because pain relief may be diminished. If an opioid is needed, it names a non-tramadol opioid as an option (Crews et al., Clinical Pharmacology & Therapeutics, 2021). The antiplatelet drug clopidogrel works in a similar way: CYP2C19 converts it into its active form.

So the same gene can push in opposite directions depending on the drug. That is why guidelines always frame their recommendations for a gene–drug pair – never for a gene in general.

Breakdown, transport, target: three ways genes have a say

Enzymes are not the only levers. Genes act at three points along a drug’s path:

Breakdown and activation: enzymes of the cytochrome P450 family such as CYP2D6, CYP2C19 and CYP2C9, plus DPYD in the breakdown of fluoropyrimidines and TPMT for thiopurines.
Transport: transporters move drugs into or out of cells. SLCO1B1, for example, forms an entrance door through which statins reach the liver.
Target structure and immune system: VKORC1 is the docking site of the anticoagulant warfarin. HLA-B helps determine whether the immune system reacts violently to certain drugs such as abacavir.

Which of these genes are needed most often in practice, and which groups of drugs they affect, is shown in Key genes: CYP2D6, CYP2C19 and more.

Almost everyone carries a variant

Does this only concern rare exceptions? The largest analysis to date gives a clear answer: no. Researchers at Stanford University analyzed the genes of 487,409 UK Biobank participants. For 14 genes covered by CPIC guidelines, 99.5% carried at least one variant that could cause an atypical response to at least one drug – on average to 10.3 drugs. Nearly 24% had already been prescribed such a drug (McInnes et al., Clinical Pharmacology & Therapeutics, 2021).

And the field is growing: especially in people of non-European ancestry, the researchers also found many variants that are likely to impair function and are not yet captured by today’s definitions. Science still has a lot to discover here.

For your practice, this means: pharmacogenetics does not concern a small group – it concerns almost everyone. Because inherited genes do not change, a result determined once can be picked up again for later prescriptions. Whether to test a full panel in advance or specifically before a drug is discussed in Pre-emptive or reactive testing?.

What research shows in routine care

Does this work beyond the university hospital? The European PREPARE study tested exactly that: 6,944 patients in seven countries, Austria among them, were tested for 12 genes before a new prescription. Among people with a relevant result for their drug, 21.0% experienced clinically relevant side effects under genotype-guided treatment, compared with 27.7% under standard care. The approach proved feasible across very different European health care systems (Swen et al., Lancet, 2023).

The logical conclusion: pharmacogenetics has arrived in routine care – in hospitals, practices and pharmacies. It delivers its value when the result is in the prescribing physician’s hands at the right moment.

What pharmacogenetics can do – and what it cannot

It adds, it does not replace: the clinical picture, lab values, drug level measurements and co-medication remain the basis of every treatment decision.
It applies to gene–drug pairs: not every drug depends on genes. Concrete recommendations exist where guidelines have formulated them (Guidelines: CPIC, DPWG and drug labels).
It shows the inborn disposition: what an inhibitor in the co-medication does to an enzyme is invisible to the genetic test. The Geneva case shows how the two interact.
It grows with knowledge: guidelines are updated continuously. In early 2026, for example, a revised CPIC guideline on thiopurines was published (Maillard et al., Clinical Pharmacology & Therapeutics, 2026).
It is a decision aid: decisions about medication – stopping, switching, changing the dose – are made by the treating physician.

How to read a pharmacogenetic result and explain it clearly to patients is shown in Understanding and communicating results.

Frequently asked questions

What does “poor metabolizer” mean?

A poor metabolizer has two gene copies that produce little or none of a particular enzyme. Drugs broken down by this enzyme stay in the body longer; prodrugs activated by it work less well. What this means for a given drug is described in the guideline for that gene–drug pair.

What is a prodrug?

A prodrug is a precursor that the body first has to convert into the actual active drug. Codeine, for example, is converted to morphine via CYP2D6, and clopidogrel is converted to its active form via CYP2C19. With prodrugs, a slow enzyme means less effect and an ultrarapid one means more.

How common are pharmacogenetic variants?

Very common. In an analysis of 487,409 UK Biobank participants, 99.5% carried a variant that could cause an atypical response to at least one drug – on average to 10.3 drugs.

Does a pharmacogenetic result change over a lifetime?

Inherited genes do not change. What can change is co-medication, kidney and liver function – and the state of knowledge, because guidelines are updated regularly. That is why it pays to look at a result in light of the current guideline whenever a new prescription comes up.

Can a pharmacogenetic result alone justify a change in treatment?

No. The result is a decision aid alongside the clinical picture, co-medication and organ function. Whether a drug is stopped, switched or dosed differently is decided solely by the treating physician.

Pharmacogenetics in your practice or pharmacy?

Tell us about your setting – we will show you how the offer can work for you.

Request a project →Offer for physicians

Note: This guide is general information for businesses and professionals and does not replace medical or legal advice. The genetic traits determined in a genetic analysis are well documented (each gene included is backed by at least three independent studies); recommendations derived from them are logical conclusions, not scientifically proven. Pharmacogenetic results do not replace a medical decision: any change to medication is made only by the treating physician. Regulations can change; errors and changes excepted.