- Munir Pirmohamed, professor of clinical pharmacology
- 1Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GL, UK
Grapefruit juice, which is widely consumed for its positive health benefits, can have severe, sometimes fatal, interactions with drugs. This phenomenon was first identified serendipitously about 20 years ago for the calcium channel antagonist felodipine,1 and a recent review found that more than 85 drugs can be affected by grapefruit juice.2 Two main mechanisms, which have different clinical consequences, have been defined (table⇓).
Firstly, grapefruit juice contains furanocoumarins (such as 6′,7′-dihydroxybergamottin),3 which can cause irreversible inhibition of the cytochrome P450 enzyme, CYP3A4, mainly in the small intestine.4 CYP3A4 is involved in the metabolism of around 50% of drugs, so a wide variety of drugs can be affected by the consumption of grapefruit juice. The net effect is a reduction in the pre-systemic metabolism of these drugs, which increases their systemic exposure, sometimes by more than 700% (as has been shown for simvastatin).5 Because inhibition of CYP3A4 is irreversible, it can last for …