More on grapefruit juice and drugs

A few weeks back, I wrote about drug interactions. On the recommendation of my editor (it was originally for the local paper,) I'd removed the details of how certain drugs are metabolized - the part I found most interesting, and the part he thought would most likely lead to bored and frustrated readers.

At the time I'd agreed with him and cut. But then, over the Thanksgiving Holiday, when I'd jokingly commented on the cranberry juice cocktail my friend was about to finish off, she said,

"...but I only take the Lipitor at night. Drinking a glass of cranberry juice during the day shouldn't matter."

Maybe, maybe not. I don't know much about the combination of Lipitor (atorvastatin calcium) and cranberry juice but the comment reminded me of why I'd written about the details of drug metabolism in the first place.

While the science of drug metabolism is complicated enough, when one adds the potential for drug-drug or drug-food interactions the level of complexity can skyrocket.

First, a quick introduction to drug metabolism. Lipitor is a drug metabolized primarily by enzymes belonging the CYP detoxification or drug metabolizing system. Years ago the CYP system was one of the few recognized detoxification systems in the body. That is, a collection of enzymes working together to metabolize toxic chemicals and send them on their way before they can cause any damage. Back then we knew of only a couple of enzymes, now there are dozens and dozens grouped into "families" of CYP enzymes. In the case of Lipitor, CYP3A4 is key for proper metabolism and eventual excretion of the drug.

For chemicals that require metabolism by CYP enzymes prior to excretion, the CYPs play an important role in determining the half-life of a drug or chemical.

Half-life refers to the length of time required for a drug or chemical to be reduced to one-half the initial concentration. Knowing the half-life is necessary to determing dosage ensuring that 1) there is sufficient levels of drug in the system and 2) concentrations don't get too high that they become toxic.

Anything that screws with the half-life of a chemical is potentially very dangerous. For chemicals that must be metabolized in order to be excreted, an increase in CYP metabolism would reduce half-life, resulting in drug concentrations that may no longer effective. Conversely, a reduction of CYP metabolism, or inhibition of metabolism can increase half-life, causing drugs to accumulate to toxic, possibly even lethal concentrations.

And even asking "what's the half-life" of a drug under normal conditions isn't so simple. Take the example of Lipitor. While the parent compound Lipitor (the actual drug that you ingest) may have a half-life of only fourteen hours, the metabolites of the drug - which in this case are most active - have a much longer half-life of twenty to thirty hours. That means that it can take up to thirty hours for half the initial concentration of active metabolites to exit your body.

Now lets consider the interaction between grapefruit juice (really certain chemicals in grapefruit juice) which act as inhibitors of CYP3A4. In this case, those CYP enzymes responsible for metabolic breakdown of Lipitor would be inhibited, essentially extending the half-life of the drug possibly leading to potentially toxic concentration of the drug.

And, what makes this all really complicated is that depending on how an inhibitor like grapefruit juice does it's dirty-work, the inhibitory effects may either very short-term or can last for days. In the case of grapefruit, according to one article in Pharmacy Times drinking grapefruit juice not only has immediate (within 30 minutes) impacts on metabolism, but, depending on how long and how much one has been drinking, inhibitory effects can last up to three days. This is because the chemicals responsible for inhibition by grapefruit juice, essentially combine irreversibly to CYP3A4, taking them out of action for good, necessitating synthesis of new enzyme.

Phew - maybe my editor was right! Well, you get the point I hope.

When taking new drugs or adding new food and beverages to your diet, it's well worth the little extra effort to inform your doctor or your pharmacist of the changes.