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Grapefruit juice and drug toxicity

Continuing his series on problem areas of drug therapy Professor Hugh McGavock discusses interactions with grapefruit juice

Continuing his series on problem areas of drug therapy Professor Hugh McGavock discusses interactions with grapefruit juice

As every clinician knows, the small intestine is not just a passive membrane. A major part of its complex function is the active absorption of nutrients, salts and some vitamins.

But what many people don't realise is that the small intestine also has a powerful drug-metabolising mechanism whose evolutionary function was to detoxify poisonous materials ingested with food, preventing their absorption and rendering them harmless. This mechanism employs enzymes identical to the drug-metabolising liver enzymes – the so-called cytochrome P450 oxidase system.

Unfortunately for the prescriber, these enzymes in the intestinal mucosa also metabolise and render impotent many important modern drugs, such as those listed in the table (see right). Drug companies are well aware of this and set the standard dose of the drugs shown at up to double the dose that would be adequate were the intestine devoid of metabolic function.

The problem

41229092A single glass of grapefruit juice, half a grapefruit or a Seville-type (bitter) orange blocks the intestinal P450 enzymes for up to 24 hours. During that period, up to double the correct dose of the drugs in the table may be absorbed into the circulation. This may lead to toxic concentrations in the tissues. Note that it doesn't matter at what time the grapefruit juice is consumed – the intestinal metabolic enzymes will be knocked out for 24 hours. Some authorities have suggested a litre of grapefruit juice must be consumed to cause this effect. This is not so – a 250ml glass is enough.

Possible solutions

The simplest way of avoiding the risks from grapefruit juice is to tell all patients taking short-term or maintenance medication to avoid it. This is no great hardship and a blunderbuss approach makes life a little easier for the prescriber and the dispenser.

A more subtle tactic is to use your prescribing software to flag up a warning message on the counterfoil of the prescription form whenever one of the relevant drugs is prescribed. This should always be accompanied by a strong verbal warning, since many patients don't read counterfoil instructions, let alone those on the patient information leaflet.

Have no illusions – the effect of grapefruit juice is a major prescribing pitfall, especially in older patients and those with reduced kidney or liver function. For the curious, the culprit in grapefruit juice has been identified as a furanocoumarin, also found in bitter oranges.

This blocks the intestinal enzymes irreversibly. But the intestinal mucosa generates a fresh population of enzyme, usually within 24 hours.

Hugh McGavock is visiting professor of prescribing science at the University of Ulster and course organiser of GP continuing clinical education at the Northern Ireland Medical and Dental Training Agency

This is an extract from Pitfalls in Prescribing and How to Avoid Them. Pulse readers can but the book at the specially discounted price of £15.00 + P&P (usual price £18.99 + P&P). To claim the discount, please visit Radcliffe Publishing and enter the discount code PPLSE9 at the checkout. Allternatively, please order via 01235 528820 quoting the same code. Offer ends 28 August 2009.

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