Garlic Reduces Saquinavir Blood Levels 50%; May Affect Other Drugs.

A study at the U.S. National Institute of Allergy and Infectious Diseases found that garlic supplements reduced blood levels of the protease inhibitor saquinavir by 51%. The garlic preparation, an amount equivalent to about two 4-gram cloves per day, was taken for 21 days by healthy HIV-negative volunteers. Then saquinavir was given for four days, and compared to a baseline four-day saquinavir dosing before the garlic was started. (1)

Later, after a 10-day washout with no saquinavir and no garlic, the volunteers were given a third 4-day dose of saquinavir. Even after 10 days off garlic, the saquinavir blood levels after a third four-day dosing only reached 60-70% of the original baseline blood levels -- indicating a persistent effect of the garlic.

Other findings of this study are complex, and the mechanism of this interaction is not clear. It probably involves the body's CYP450 enzyme system, yet the garlic appears to be affecting the oral bioavailability of saquinavir, not its elimination from the body. And there were two distinct groups of volunteers in how the garlic affected them. Most had a big decline in saquinavir levels after the 21 days of garlic use, with good recovery after the 10-day washout period. But three volunteers did not have a significant decline in saquinavir blood levels during the 21 days of garlic use -- but did have a big drop after the washout.

It is not clear how other drugs besides saquinavir will be affected. One study failed to find a statistically significant interaction with ritonavir, which affects the CYP450 enzyme system differently; however, that study used only four days of garlic treatment.

Saquinavir study co-author Judith Falloon, M.D., said, "We saw a definite, prolonged interaction. The clear implication is that doctors and patients should be cautious about using garlic supplements during HIV therapy."

Comment: Do Companies Care If Their Drugs Work?

Clearly we need more drug interaction studies to guide physicians and patients in how to use medications -- especially when there is reason to suspect an interaction, or when a supplement is in wide use by those taking a certain medication. Drug interaction studies are usually small, inexpensive, and easy to do; this one, for example, had only 10 volunteers (six women and four men -- one woman was excluded from analysis due to lack of adherence), and each volunteer took the drug for a total of 12 days, reducing both side effects and expense.

We are fortunate that the U.S. National Institutes of Health tested garlic, a supplement widely used by people with HIV -- and found that it cut blood levels of saquinavir in half. This interaction could lead to drug failure and development of viral resistance, just as if patients cut their doses in half before taking them. Effects of garlic (and most other supplements) on other protease inhibitors are currently unknown.

While NIH should be commended, we need to ask why manufacturers don't do more interaction testing as a matter of course. Antiretrovirals are premium products with huge profit margins, costing thousands of dollars a year -- prices supposedly financing research and development. And more importantly, these are critical medicines that can determine whether patients live or die.

Yes, there are many supplements and even more approved drugs, but not very many are widely used by persons with HIV. And serious interactions are often fairly predictable from what is already known about the pharmacology of the drugs and supplements. Interaction testing is usually fast and cheap -- and none need be done on antiretrovirals that don't make it, only on those soon to be approved and marketed. What is needed is ongoing strategic initiative to identify potentially serious problems and spend a little money to head them off before they happen -- not years later.

Aside from the impact on human health, testing the most obvious potential interactions would contribute to the bottom line. Companies don't benefit when their drugs fail and patients stop using them, and their doctors and other doctors become less likely to choose those drugs for other patients. After paying all the costs of developing antiretrovirals and marketing them, when companies finally get a chance to make a profit, they are throwing much of it away.

The problem is that corporations do not act in their long-term interests unless they are organized to do so. Groups within companies are afraid of generating bad news. They may not realize that this bad news is really good news, because it allows them to make their drug more successful in the real world by targeting those patients most likely to benefit.

References

(1.) Piscatelli SC, Burstein AH, Welden N, Gallicano KD and Falloon J. The Effects of Garlic Supplements on the Pharmacokinetics of Saquinavir. Clinical Infectious Diseases. January 15, 2001; volume 34.