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Rich66 09-07-2008 12:13 PM

Absorption of Lapatinib
 
A sour mix: Grapefruit is just one of the juices that reduces absorption of drugs, study says



http://www.nj.com/business/index.ssf...is_just_1.html

by George E. Jordan/The Star-Ledger Saturday September 06, 2008, 3:00 PM


The medical world was stunned -- and initially quite skeptical -- when a University of Western Ontario pharmacologist in the early 1990s announced the discovery of the so-called grapefruit juice effect.
The researcher, David Bailey, claimed a glass of grapefruit juice could boost, two- to three-fold, the potency of a wide variety of commonly prescribed medicines, including the cholesterol fighter Lipitor, the world's biggest-selling drug.
Today, 48 drugs ranging from cholesterol-lowering statins to cancer therapies such as Gleevec carry a warning grapefruit juice may turn a safe dose of medicine into an overdose, according to the American Academy of Family Physicians.

Soon, there could be even more.
This summer, Bailey announced his latest findings: Grapefruit juice, as well as apple and orange juice, also can have the opposite effect. A series of studies, he said, found these fruit juices dramatically cut the body's absorption of certain cancer, blood pressure and cholesterol drugs, as well as antihistamines such as Allegra.
Healthy volunteers who took Allegra with grapefruit, apple or orange juice, for example, absorbed only half the amount of the drug, compared with volunteers who took the medicine with water.
"Most people have not thought of this," Bailey said last week from his office in London, Ontario, 120 miles southwest of Toronto. "We talk about drug interactions, but food-drug interactions is kind of passe, not a big concern."
A DOSE OF CHANGE, MAYBE
Bailey's findings, the experts say, have the potential to change medical practices, such as altering the way millions of patients are instructed to take medication. What is more, pharmaceutical companies and drug researchers already are studying grapefruit as a way to cut medicine costs by boosting the effectiveness of smaller doses of expensive cancer drugs.
The studies suggest drinking fruit juices to wash down your pills at breakfast may not be a good idea, he said. Fruit juice drinkers probably should wait a minimum of two hours after taking their medications, he said.
"If half your prescription drug isn't absorbed because you took it with a glass of orange juice, that's a profound effect," he said.
Although Bailey's findings have been documented in four studies published in scholarly journals since 2002, they have had little effect so far in the medical community.
Randolph Modlin, a leading heart researcher and chief of cardiology at Walter Reed Army Medical Center in Washington, D.C., said he already counsels patients about grapefruit juice. But "on issues of apple juice and orange juice -- no, I need to learn more about this."
"That's news to me," said cardiologist Douglas Zipes, professor emeritus of medicine, pharmacology and toxicology at Indiana University School of Medicine. "It make sense. Anything you ingest could affect absorption or the enzyme systems in the body."
With grapefruit juice, organic chemicals called furanocoumarins cause more prescription medicine to enter the bloodstream faster, according to Bailey's studies. It has a particularly powerful effect on anti-cholesterol statins and beta-blockers taken daily by millions of sufferers of hypertension and irregular heartbeats.
As a result, taking one tablet of cholesterol medicine with a glass of grapefruit juice, according to Bailey, could have the same potency as a dozen tablets taken with water.
THE FRUITS OF RESEARCH
Bailey presented a summary of his latest research on apple and orange juice at the American Chemical Society conference last month in Philadelphia. It found the juices block proteins in the intestine, known as transporters, that shuttle pharmaceuticals through the gastrointestinal tract and into the bloodstream.
"It doesn't effect all drugs, but it effects enough of them for pharmaceutical companies to consider them and for the FDA to consider a juice study as part of the development process," Bailey said.
The grapefruit juice effect didn't gain traction until it was published in the Lancet, a respected medical journal. Apple and orange juice could soon gain similar attention because Bailey edits a section of the annual Canadian drug information and safety manual.
Marc Cohen, chief cardiologist at Newark Beth Israel Medical Center, said the latest research into grapefruit, apple and orange juice will not be widely accepted by doctors until it is verified in a large-scale clinical trial.
"There might be measurements we can do in a test tube, but at the end of the day, does that translate into more heart or fewer heart attacks, more hospital stays or fewer hospital stays?" Cohen said. "What you really want to know is if there was enough interference that the clinical effect of the drug was lost."
Bailey's findings are largely based on experiments involving fewer than 100 test subjects. Large-scale clinical trials typically involve hundreds of volunteers that span gender, race, geography and socioeconomic strata.
WHO'S GETTING A BOOST
So far, the grapefruit juice effect appears to have had little effect on the pharmaceutical industry, since sales of statins have continued to grow steadily. The fruit industry is another story.
Since the grapefruit juice effect became widely publicized, sales of grapefruit juice have steadily declined, down nearly 40 percent since 2003, according to the Florida Department of Citrus.
Medical researchers have been fascinated by the grapefruit juice effect, and not only as an "adverse" effect on dosing. University of Chicago research oncologists Mark Ratain and Ezra Cohen want to exploit juice as a way to reduce the costs of prescription medicine.
They presented a study in July at the American Society of Clinical Oncology that claims patients on the cancer drug lapatinib, which costs $3,000 a month, could save as much as half the cost by boosting the drug's absorption with grapefruit juice. The strategy, they said, would cut costs by reducing the necessary dose as well as help ease lapatinib's main side effect: severe diarrhea caused by unabsorbed drug in the gut.
Pharmaceutical companies also are getting into the act, tinkering with so-called "value meals" that can increase the effectiveness of some costly cancer drugs.
GlaxoSmithKline recently found that the body's absorption of its cancer therapy Tykerb increased 167 percent when taken with a low-fat meal, compared with taking the drug on an empty stomach. A high-fat meal, the study found, increased its absorption by 325 percent.
The newest studies by Ratain and Cohen seek to take it to the next level: Wash down the high-fat food with a tall glass of grapefruit juice.

chrisy 09-07-2008 06:28 PM

I think the study says that grapefruit juice INCREASES the absorption.

This study caused quite a stir when it came out. At the time I was on Tykerb and I asked my oncologist about the study. Although it is true that grapefruit juice (and maybe other things) affect the absorption rate, each person's metabolism is different. So tinkering with absorption rates could be dangerous as you wouldn't really know how much you were getting.

That said, it would be nice if this area could be more fully investigated because these drugs are definitely expensive - and if you could really control/adjust the dose by adding specific foods, that would be great. I'm not a "big pharma" conspiracy theory person - I LOVE Genentech (and also GSK the maker of lapatinib) and hope to be one of their labrats for a lot more years - but I am skeptical that these studies would be a funding priority for THEM. But I'd sure like to see more of this type of research!

Rich66 09-08-2008 10:33 AM

Maximizing absorption could also reduce the side effects from malabsorption. But I like that idea of yours that you could get more "bang for your buck" by taking the meds with certain foods.

hutchibk 09-08-2008 12:13 PM

One of the challenges of the 'theory of food combining with meds' is the question of adherence or compliance by the patient to the exact discipline necessary to not cause unintended consequences.


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