Many drugs are metabolised in the liver. Drugs are either metabolised by phase I reactions (oxidation, reduction, or hydrolysis) or phase II reactions (e.g. glucuronidation).

Phase I reactions are mainly carried out by the cytochrome P450 family of isoenzymes, of which CYP3A4 is the most important isoenzyme involved in the metabolism of drugs. Induction of cytochrome P450 isoenzymes by one drug can increase the rate of metabolism of another, resulting in lower plasma concentrations and a reduced effect. On withdrawal of the inducing drug, plasma concentrations increase, and toxicity can occur.

Conversely, when one drug inhibits cytochrome P450 isoenzymes, it can decrease the metabolism of another, leading to higher plasma concentrations, resulting in an increased effect with a risk of toxicity.

Isoenzymes of the hepatic cytochrome P450 system interact with a wide range of drugs. With knowledge of which isoenzymes are involved in a drug’s metabolism, it is possible to predict whether certain pharmacokinetic interactions will occur.

Less is known about the enzymes involved in phase II reactions. These include UDP-glucuronyltransferases which, for example, might be induced by rifampicin, resulting in decreased metabolism of mycophenolate (a substrate for this enzyme) to its active form mycophenolic acid.


The mnemonic PC BRASS can be used to memorise the commonly encountered cytochrome p450 enzyme inducers:

P – Phenytoin

C – Carbamazepine

B – Barbiturates

R – Rifampicin

A – Alcohol (chronic ingestion)

S – Sulphonylureas

S – Smoking


The mnemonic O DEVICES can be used to memorise the commonly encountered cytochrome p450 enzyme inhibitors:

O – Omeprazole

D – Disulfiram

E – Erythromycin (And other macrolide antibiotics)

V – Valproate (sodium valproate)

I – Isoniazid

C – Ciprofloxacin

E – Ethanol (acute ingestion)

S – Sulphonamides



Header image used on licence from Shutterstock

Thank you to the joint editorial team of for this article.