I’ll have the gralefrit please. Followed by the balm carousel.

Obviously the death of Michael Jackson is very sad. For three young children to lose a father is a tragedy, and one must feel for them and the remaining Jackson siblings. It is sad to note that they appear to want to lay blame somewhere (which may or may not be justified, and may or may not lie with his doctor) when I can’t help but feel if Jackson had received help from his family 25 years ago then his might have been avoided.

What I found interesting was a story I found in the Metro this morning, suggesting his grapefruit intake may be responsible in a way. This is not the first instance of such a thing, either. The mechanism of action is interesting, and one that has been of great interest to the pharmaceutical industry for some time: grapefruit juice, or at least one of its components, is a potent cytochrome P450 inhibitor. The P450 enzymes are heavily involved with one of the major pathways of drug metabolism, and make up a substantial part of the screening cascade.

The triazole antifungals were the drug family that first brought the P450 enzymes to people’s attention (if memory serves). Several studies were carried out looking at fluconazole and voriconazole and their breakdown pathway (P450, needless to say) but interestingly voriconazole (Vfend) also activates the P450 pathway, that is to say it contributes to its own clearance. Studies with Vfend and grapefruit juice show that the half life of Vfend is greatly improved.

Antifungals are not the only drug class that are affected. Various HIV drugs, the antiarrhythmic amiodarone, and as is now apparent to the general media, painkillers.

Only a few drugs have this potential interaction highlighted, but surely all prescription only medicines should point out the risks not just of drug-drug interactions but drug-diet as well. Not all drugs would display this, nor would all patients. But if clinical science wants to tailor therapies for the individual then at least the potential risk should be pointed out to everyone given a prescription-only-medicine. It may take the tragic death of one of the most popular entertainers of the late 20th century to bring this about.

And the Gralefrit reference? Fawlty Towers, I'm afraid.